Ignet

Gene Information

Gene symbol: DUSP1

Gene name: dual specificity phosphatase 1

HGNC ID: 3064

Synonyms: HVH1, CL100, MKP-1

Related Genes

#	Gene Symbol	Number of hits
1	ACTB	1 hits
2	ADIPOQ	1 hits
3	AGT	1 hits
4	AKT1	1 hits
5	CCL2	1 hits
6	CCRK	1 hits
7	CDC25B	1 hits
8	CDC25C	1 hits
9	CREB1	1 hits
10	GAP43	1 hits
11	GLRX	1 hits
12	ID1	1 hits
13	IFI44	1 hits
14	IGF1	1 hits
15	IL1B	1 hits
16	INPP5D	1 hits
17	INS	1 hits
18	INSIG1	1 hits
19	JUN	1 hits
20	MAP2K3	1 hits
21	MAPK1	1 hits
22	MAPK10	1 hits
23	MAPK14	1 hits
24	MAPK3	1 hits
25	MAPK6	1 hits
26	MAPK8	1 hits
27	NOS2A	1 hits
28	NOX4	1 hits
29	PCK2	1 hits
30	PDGFA	1 hits
31	PIK3CA	1 hits
32	PIK3CG	1 hits
33	PPARGC1A	1 hits
34	PPP1CA	1 hits
35	PPP1R3C	1 hits
36	PTHLH	1 hits
37	PTPN1	1 hits
38	PTPRU	1 hits
39	SLC2A1	1 hits
40	SLC37A4	1 hits
41	THBS1	1 hits
42	USP2	1 hits

Related Sentences

#	PMID	Sentence
1	7485483	These include altered expression of insulin-regulated genes such as glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate carboxykinase (PEPCK), and beta-actin, and genes such as CL-6 and map kinase phosphatase-1 (MKP-1) that were previously unlinked to insulin action in animals.
2	7485483	Abnormal elevation of mRNAs encoding G-6-Pase, MKP-1, and PEPCK in the time 0 diabetic liver results in decreased induction after partial hepatectomy.
3	7485483	Other genes, such as CL-6 and beta-actin, are induced at a lower level in the hepatectomized diabetic animals.
4	7485483	These include altered expression of insulin-regulated genes such as glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate carboxykinase (PEPCK), and beta-actin, and genes such as CL-6 and map kinase phosphatase-1 (MKP-1) that were previously unlinked to insulin action in animals.
5	7485483	Abnormal elevation of mRNAs encoding G-6-Pase, MKP-1, and PEPCK in the time 0 diabetic liver results in decreased induction after partial hepatectomy.
6	7485483	Other genes, such as CL-6 and beta-actin, are induced at a lower level in the hepatectomized diabetic animals.
7	9688833	In this study, we examined the contribution of MAPK pathway in insulin-stimulated mitogenesis using primary vascular smooth muscle cells (VSMCs) isolated from aortas of normotensive Wistar-Kyoto rats (WKY) and spontaneous hypertensive rats (SHR).
8	9688833	VSMCs were grown to confluence in culture, serum starved, and examined for DNA synthesis (using [3H]thymidine (TDR), immunoprecipitated MAPK activity, and MAPK phosphatase (MKP-1) induction).
9	9688833	Pretreatment with insulin-like growth factor I (IGF-I) receptor antibody did not abolish mitogenesis mediated by 10-100 nM insulin, suggesting that insulin effect is mediated via its own receptors.
10	9688833	Insulin-stimulated mitogenesis was accompanied by a dose-dependent increase in MAPK activity in SHR, with a peak activation (>2-fold over basal) between 5 and 10 min with 100 nM insulin.
11	9688833	Insulin had very small effects on MAPK activity in WKY.
12	9688833	Pretreatment with MEK inhibitor, PD-98059, completely blocked insulin's effect on MAPK activation and mitogenesis.
13	9688833	Inhibition of phosphatidylinositol 3-kinase with wortmannin also prevented insulin's effects on MAPK activation and mitogenesis.
14	9688833	In WKY, insulin and IGF-I treatment resulted in a rapid induction of MKP-1, the dual-specificity MAPK phosphatase.
15	9688833	We conclude that insulin is mitogenic in SHR, and the effect appears to be mediated by sustained MAPK activation due to impaired insulin-mediated MKP-1 mRNA expression, which may act as an inhibitory feedback loop in attenuating MAPK signaling.
16	9688833	In this study, we examined the contribution of MAPK pathway in insulin-stimulated mitogenesis using primary vascular smooth muscle cells (VSMCs) isolated from aortas of normotensive Wistar-Kyoto rats (WKY) and spontaneous hypertensive rats (SHR).
17	9688833	VSMCs were grown to confluence in culture, serum starved, and examined for DNA synthesis (using [3H]thymidine (TDR), immunoprecipitated MAPK activity, and MAPK phosphatase (MKP-1) induction).
18	9688833	Pretreatment with insulin-like growth factor I (IGF-I) receptor antibody did not abolish mitogenesis mediated by 10-100 nM insulin, suggesting that insulin effect is mediated via its own receptors.
19	9688833	Insulin-stimulated mitogenesis was accompanied by a dose-dependent increase in MAPK activity in SHR, with a peak activation (>2-fold over basal) between 5 and 10 min with 100 nM insulin.
20	9688833	Insulin had very small effects on MAPK activity in WKY.
21	9688833	Pretreatment with MEK inhibitor, PD-98059, completely blocked insulin's effect on MAPK activation and mitogenesis.
22	9688833	Inhibition of phosphatidylinositol 3-kinase with wortmannin also prevented insulin's effects on MAPK activation and mitogenesis.
23	9688833	In WKY, insulin and IGF-I treatment resulted in a rapid induction of MKP-1, the dual-specificity MAPK phosphatase.
24	9688833	We conclude that insulin is mitogenic in SHR, and the effect appears to be mediated by sustained MAPK activation due to impaired insulin-mediated MKP-1 mRNA expression, which may act as an inhibitory feedback loop in attenuating MAPK signaling.
25	9688833	In this study, we examined the contribution of MAPK pathway in insulin-stimulated mitogenesis using primary vascular smooth muscle cells (VSMCs) isolated from aortas of normotensive Wistar-Kyoto rats (WKY) and spontaneous hypertensive rats (SHR).
26	9688833	VSMCs were grown to confluence in culture, serum starved, and examined for DNA synthesis (using [3H]thymidine (TDR), immunoprecipitated MAPK activity, and MAPK phosphatase (MKP-1) induction).
27	9688833	Pretreatment with insulin-like growth factor I (IGF-I) receptor antibody did not abolish mitogenesis mediated by 10-100 nM insulin, suggesting that insulin effect is mediated via its own receptors.
28	9688833	Insulin-stimulated mitogenesis was accompanied by a dose-dependent increase in MAPK activity in SHR, with a peak activation (>2-fold over basal) between 5 and 10 min with 100 nM insulin.
29	9688833	Insulin had very small effects on MAPK activity in WKY.
30	9688833	Pretreatment with MEK inhibitor, PD-98059, completely blocked insulin's effect on MAPK activation and mitogenesis.
31	9688833	Inhibition of phosphatidylinositol 3-kinase with wortmannin also prevented insulin's effects on MAPK activation and mitogenesis.
32	9688833	In WKY, insulin and IGF-I treatment resulted in a rapid induction of MKP-1, the dual-specificity MAPK phosphatase.
33	9688833	We conclude that insulin is mitogenic in SHR, and the effect appears to be mediated by sustained MAPK activation due to impaired insulin-mediated MKP-1 mRNA expression, which may act as an inhibitory feedback loop in attenuating MAPK signaling.
34	9737976	Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells.
35	9737976	In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures.
36	9737976	Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression.
37	9737976	Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression.
38	9737976	Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production.
39	9737976	Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression.
40	9737976	To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK.
41	9737976	These inhibitors abolished the effect of insulin on MKP-1 expression.
42	9737976	Only PD98059 inhibited insulin-mediated iNOS protein induction.
43	9737976	Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity.
44	9737976	We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.
45	9737976	Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells.
46	9737976	In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures.
47	9737976	Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression.
48	9737976	Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression.
49	9737976	Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production.
50	9737976	Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression.
51	9737976	To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK.
52	9737976	These inhibitors abolished the effect of insulin on MKP-1 expression.
53	9737976	Only PD98059 inhibited insulin-mediated iNOS protein induction.
54	9737976	Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity.
55	9737976	We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.
56	9737976	Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells.
57	9737976	In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures.
58	9737976	Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression.
59	9737976	Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression.
60	9737976	Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production.
61	9737976	Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression.
62	9737976	To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK.
63	9737976	These inhibitors abolished the effect of insulin on MKP-1 expression.
64	9737976	Only PD98059 inhibited insulin-mediated iNOS protein induction.
65	9737976	Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity.
66	9737976	We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.
67	9737976	Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells.
68	9737976	In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures.
69	9737976	Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression.
70	9737976	Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression.
71	9737976	Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production.
72	9737976	Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression.
73	9737976	To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK.
74	9737976	These inhibitors abolished the effect of insulin on MKP-1 expression.
75	9737976	Only PD98059 inhibited insulin-mediated iNOS protein induction.
76	9737976	Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity.
77	9737976	We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.
78	9737976	Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells.
79	9737976	In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures.
80	9737976	Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression.
81	9737976	Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression.
82	9737976	Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production.
83	9737976	Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression.
84	9737976	To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK.
85	9737976	These inhibitors abolished the effect of insulin on MKP-1 expression.
86	9737976	Only PD98059 inhibited insulin-mediated iNOS protein induction.
87	9737976	Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity.
88	9737976	We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.
89	9737976	Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells.
90	9737976	In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures.
91	9737976	Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression.
92	9737976	Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression.
93	9737976	Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production.
94	9737976	Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression.
95	9737976	To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK.
96	9737976	These inhibitors abolished the effect of insulin on MKP-1 expression.
97	9737976	Only PD98059 inhibited insulin-mediated iNOS protein induction.
98	9737976	Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity.
99	9737976	We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.
100	9737976	Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells.
101	9737976	In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures.
102	9737976	Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression.
103	9737976	Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression.
104	9737976	Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production.
105	9737976	Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression.
106	9737976	To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK.
107	9737976	These inhibitors abolished the effect of insulin on MKP-1 expression.
108	9737976	Only PD98059 inhibited insulin-mediated iNOS protein induction.
109	9737976	Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity.
110	9737976	We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.
111	9737976	Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells.
112	9737976	In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures.
113	9737976	Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression.
114	9737976	Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression.
115	9737976	Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production.
116	9737976	Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression.
117	9737976	To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK.
118	9737976	These inhibitors abolished the effect of insulin on MKP-1 expression.
119	9737976	Only PD98059 inhibited insulin-mediated iNOS protein induction.
120	9737976	Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity.
121	9737976	We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.
122	10203357	Protein kinase C (PKC), an enzyme known to be stimulated in DM, also activates MAPK.
123	10203357	MAPK activity, measured as myelin basic protein kinase, was elevated by approximately 50% in DM versus controls (CON).
124	10203357	Increased protein contents of p42mapk and p44mapk, as well as increased tyrosine phosphorylation and mobility shift of p42mapk, were also observed in DM.
125	10203357	Protein expression of MAPK phosphatase-1 (MKP-1), a dual specificity phosphatase that inactivates MAPK, was approximately 60% of CON.
126	10203357	These results demonstrate that glomerular MAPK is activated in DM by multiple mechanisms i.e., increases in protein contents, increased phosphorylation, and decreased dephosphorylation of the enzyme due to suppression of MKP-1.
127	10203357	Protein kinase C (PKC), an enzyme known to be stimulated in DM, also activates MAPK.
128	10203357	MAPK activity, measured as myelin basic protein kinase, was elevated by approximately 50% in DM versus controls (CON).
129	10203357	Increased protein contents of p42mapk and p44mapk, as well as increased tyrosine phosphorylation and mobility shift of p42mapk, were also observed in DM.
130	10203357	Protein expression of MAPK phosphatase-1 (MKP-1), a dual specificity phosphatase that inactivates MAPK, was approximately 60% of CON.
131	10203357	These results demonstrate that glomerular MAPK is activated in DM by multiple mechanisms i.e., increases in protein contents, increased phosphorylation, and decreased dephosphorylation of the enzyme due to suppression of MKP-1.
132	10644515	High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation.
133	10644515	Our laboratory has recently demonstrated a role for the phosphatidylinositol 3-kinase-mediated inducible NO synthase (iNOS) signaling pathway in acute regulation of insulin-induced mitogen-activated protein phosphatase-1 (MKP-1) expression in primary cultures of rat aortic vascular smooth muscle cells (VSMCs) (N.
134	10644515	We now show that prolonged treatment of VSMCs with 100 nM insulin and high glucose (25 mM) for 12-24 h, to mimic hyperinsulinemia and hyperglycemia, completely blocked MKP-1 mRNA and protein expression in response to subsequent acute insulin treatment.
135	10644515	To understand the mechanism of insulin resistance induced by high glucose and insulin, we studied the regulation of iNOS protein induction in these cells.
136	10644515	Both high glucose and chronic insulin treatment caused a marked impairment of iNOS induction in response to acute insulin.
137	10644515	Blocking of signaling via the p38 mitogen-activated protein kinase (MAPK) pathway by prior treatment for 1 h with SB-203580, a synthetic p38 MAPK inhibitor, completely prevented the inhibition of iNOS induced by high glucose and insulin and restored MKP-1 induction to levels observed with acute insulin treatment.
138	10644515	Furthermore, high glucose and chronic insulin treatment caused sustained p38 MAPK activation.
139	10644515	We conclude 1) that chronic insulin and high glucose-induced insulin resistance is accompanied by marked reductions in both iNOS and MKP-1 inductions due to p38 MAPK activation that leads to excessive cell growth and 2) that p38 MAPK/extracellular signal-regulated kinase pathways regulate iNOS induction, thereby controlling MKP-1 expression, which in turn inactivates MAPKs as a feedback mechanism and inhibits cell growth.
140	10644515	High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation.
141	10644515	Our laboratory has recently demonstrated a role for the phosphatidylinositol 3-kinase-mediated inducible NO synthase (iNOS) signaling pathway in acute regulation of insulin-induced mitogen-activated protein phosphatase-1 (MKP-1) expression in primary cultures of rat aortic vascular smooth muscle cells (VSMCs) (N.
142	10644515	We now show that prolonged treatment of VSMCs with 100 nM insulin and high glucose (25 mM) for 12-24 h, to mimic hyperinsulinemia and hyperglycemia, completely blocked MKP-1 mRNA and protein expression in response to subsequent acute insulin treatment.
143	10644515	To understand the mechanism of insulin resistance induced by high glucose and insulin, we studied the regulation of iNOS protein induction in these cells.
144	10644515	Both high glucose and chronic insulin treatment caused a marked impairment of iNOS induction in response to acute insulin.
145	10644515	Blocking of signaling via the p38 mitogen-activated protein kinase (MAPK) pathway by prior treatment for 1 h with SB-203580, a synthetic p38 MAPK inhibitor, completely prevented the inhibition of iNOS induced by high glucose and insulin and restored MKP-1 induction to levels observed with acute insulin treatment.
146	10644515	Furthermore, high glucose and chronic insulin treatment caused sustained p38 MAPK activation.
147	10644515	We conclude 1) that chronic insulin and high glucose-induced insulin resistance is accompanied by marked reductions in both iNOS and MKP-1 inductions due to p38 MAPK activation that leads to excessive cell growth and 2) that p38 MAPK/extracellular signal-regulated kinase pathways regulate iNOS induction, thereby controlling MKP-1 expression, which in turn inactivates MAPKs as a feedback mechanism and inhibits cell growth.
148	10644515	High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation.
149	10644515	Our laboratory has recently demonstrated a role for the phosphatidylinositol 3-kinase-mediated inducible NO synthase (iNOS) signaling pathway in acute regulation of insulin-induced mitogen-activated protein phosphatase-1 (MKP-1) expression in primary cultures of rat aortic vascular smooth muscle cells (VSMCs) (N.
150	10644515	We now show that prolonged treatment of VSMCs with 100 nM insulin and high glucose (25 mM) for 12-24 h, to mimic hyperinsulinemia and hyperglycemia, completely blocked MKP-1 mRNA and protein expression in response to subsequent acute insulin treatment.
151	10644515	To understand the mechanism of insulin resistance induced by high glucose and insulin, we studied the regulation of iNOS protein induction in these cells.
152	10644515	Both high glucose and chronic insulin treatment caused a marked impairment of iNOS induction in response to acute insulin.
153	10644515	Blocking of signaling via the p38 mitogen-activated protein kinase (MAPK) pathway by prior treatment for 1 h with SB-203580, a synthetic p38 MAPK inhibitor, completely prevented the inhibition of iNOS induced by high glucose and insulin and restored MKP-1 induction to levels observed with acute insulin treatment.
154	10644515	Furthermore, high glucose and chronic insulin treatment caused sustained p38 MAPK activation.
155	10644515	We conclude 1) that chronic insulin and high glucose-induced insulin resistance is accompanied by marked reductions in both iNOS and MKP-1 inductions due to p38 MAPK activation that leads to excessive cell growth and 2) that p38 MAPK/extracellular signal-regulated kinase pathways regulate iNOS induction, thereby controlling MKP-1 expression, which in turn inactivates MAPKs as a feedback mechanism and inhibits cell growth.
156	10644515	High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation.
157	10644515	Our laboratory has recently demonstrated a role for the phosphatidylinositol 3-kinase-mediated inducible NO synthase (iNOS) signaling pathway in acute regulation of insulin-induced mitogen-activated protein phosphatase-1 (MKP-1) expression in primary cultures of rat aortic vascular smooth muscle cells (VSMCs) (N.
158	10644515	We now show that prolonged treatment of VSMCs with 100 nM insulin and high glucose (25 mM) for 12-24 h, to mimic hyperinsulinemia and hyperglycemia, completely blocked MKP-1 mRNA and protein expression in response to subsequent acute insulin treatment.
159	10644515	To understand the mechanism of insulin resistance induced by high glucose and insulin, we studied the regulation of iNOS protein induction in these cells.
160	10644515	Both high glucose and chronic insulin treatment caused a marked impairment of iNOS induction in response to acute insulin.
161	10644515	Blocking of signaling via the p38 mitogen-activated protein kinase (MAPK) pathway by prior treatment for 1 h with SB-203580, a synthetic p38 MAPK inhibitor, completely prevented the inhibition of iNOS induced by high glucose and insulin and restored MKP-1 induction to levels observed with acute insulin treatment.
162	10644515	Furthermore, high glucose and chronic insulin treatment caused sustained p38 MAPK activation.
163	10644515	We conclude 1) that chronic insulin and high glucose-induced insulin resistance is accompanied by marked reductions in both iNOS and MKP-1 inductions due to p38 MAPK activation that leads to excessive cell growth and 2) that p38 MAPK/extracellular signal-regulated kinase pathways regulate iNOS induction, thereby controlling MKP-1 expression, which in turn inactivates MAPKs as a feedback mechanism and inhibits cell growth.
164	10644515	High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation.
165	10644515	Our laboratory has recently demonstrated a role for the phosphatidylinositol 3-kinase-mediated inducible NO synthase (iNOS) signaling pathway in acute regulation of insulin-induced mitogen-activated protein phosphatase-1 (MKP-1) expression in primary cultures of rat aortic vascular smooth muscle cells (VSMCs) (N.
166	10644515	We now show that prolonged treatment of VSMCs with 100 nM insulin and high glucose (25 mM) for 12-24 h, to mimic hyperinsulinemia and hyperglycemia, completely blocked MKP-1 mRNA and protein expression in response to subsequent acute insulin treatment.
167	10644515	To understand the mechanism of insulin resistance induced by high glucose and insulin, we studied the regulation of iNOS protein induction in these cells.
168	10644515	Both high glucose and chronic insulin treatment caused a marked impairment of iNOS induction in response to acute insulin.
169	10644515	Blocking of signaling via the p38 mitogen-activated protein kinase (MAPK) pathway by prior treatment for 1 h with SB-203580, a synthetic p38 MAPK inhibitor, completely prevented the inhibition of iNOS induced by high glucose and insulin and restored MKP-1 induction to levels observed with acute insulin treatment.
170	10644515	Furthermore, high glucose and chronic insulin treatment caused sustained p38 MAPK activation.
171	10644515	We conclude 1) that chronic insulin and high glucose-induced insulin resistance is accompanied by marked reductions in both iNOS and MKP-1 inductions due to p38 MAPK activation that leads to excessive cell growth and 2) that p38 MAPK/extracellular signal-regulated kinase pathways regulate iNOS induction, thereby controlling MKP-1 expression, which in turn inactivates MAPKs as a feedback mechanism and inhibits cell growth.
172	11238524	Thus, we sought to determine in circulating monocytes: 1) the role of hyperglycemia in ERKs activity and phosphorylation, and 2) whether hyperglycemia affects mitogen-activated protein kinase kinase (MEK) activity and mitogen-activated protein phosphatase-1 (MKP-1) expression.
173	12176727	Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs.
174	12176727	Platelet-derived growth factor (PDGF) increased VSMC migration, which was inhibited by pretreatment with insulin in a dose-dependent manner.
175	12176727	Insulin also caused a 60% decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK) phosphorylation and activation.
176	12176727	Insulin inhibition of MAPK was accompanied by a rapid induction of MAPK phosphatase (MKP-1), which inactivates MAPKs by dephosphorylation.
177	12176727	Pretreatment with inhibitors of the nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration.
178	12176727	In contrast, adenoviral infection of VSMCs with MKP-1 or cGMP-dependent protein kinase Ialpha (cGK Ialpha), the downstream effector of cGMP signaling, blocked the activation of MAPK and prevented PDGF-directed VSMC migration.
179	12176727	Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPK phosphorylation.
180	12176727	We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Ialpha induction of MKP-1 and consequent inactivation of MAPKs.
181	12176727	Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs.
182	12176727	Platelet-derived growth factor (PDGF) increased VSMC migration, which was inhibited by pretreatment with insulin in a dose-dependent manner.
183	12176727	Insulin also caused a 60% decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK) phosphorylation and activation.
184	12176727	Insulin inhibition of MAPK was accompanied by a rapid induction of MAPK phosphatase (MKP-1), which inactivates MAPKs by dephosphorylation.
185	12176727	Pretreatment with inhibitors of the nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration.
186	12176727	In contrast, adenoviral infection of VSMCs with MKP-1 or cGMP-dependent protein kinase Ialpha (cGK Ialpha), the downstream effector of cGMP signaling, blocked the activation of MAPK and prevented PDGF-directed VSMC migration.
187	12176727	Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPK phosphorylation.
188	12176727	We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Ialpha induction of MKP-1 and consequent inactivation of MAPKs.
189	12176727	Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs.
190	12176727	Platelet-derived growth factor (PDGF) increased VSMC migration, which was inhibited by pretreatment with insulin in a dose-dependent manner.
191	12176727	Insulin also caused a 60% decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK) phosphorylation and activation.
192	12176727	Insulin inhibition of MAPK was accompanied by a rapid induction of MAPK phosphatase (MKP-1), which inactivates MAPKs by dephosphorylation.
193	12176727	Pretreatment with inhibitors of the nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration.
194	12176727	In contrast, adenoviral infection of VSMCs with MKP-1 or cGMP-dependent protein kinase Ialpha (cGK Ialpha), the downstream effector of cGMP signaling, blocked the activation of MAPK and prevented PDGF-directed VSMC migration.
195	12176727	Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPK phosphorylation.
196	12176727	We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Ialpha induction of MKP-1 and consequent inactivation of MAPKs.
197	12176727	Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs.
198	12176727	Platelet-derived growth factor (PDGF) increased VSMC migration, which was inhibited by pretreatment with insulin in a dose-dependent manner.
199	12176727	Insulin also caused a 60% decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK) phosphorylation and activation.
200	12176727	Insulin inhibition of MAPK was accompanied by a rapid induction of MAPK phosphatase (MKP-1), which inactivates MAPKs by dephosphorylation.
201	12176727	Pretreatment with inhibitors of the nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration.
202	12176727	In contrast, adenoviral infection of VSMCs with MKP-1 or cGMP-dependent protein kinase Ialpha (cGK Ialpha), the downstream effector of cGMP signaling, blocked the activation of MAPK and prevented PDGF-directed VSMC migration.
203	12176727	Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPK phosphorylation.
204	12176727	We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Ialpha induction of MKP-1 and consequent inactivation of MAPKs.
205	12176727	Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs.
206	12176727	Platelet-derived growth factor (PDGF) increased VSMC migration, which was inhibited by pretreatment with insulin in a dose-dependent manner.
207	12176727	Insulin also caused a 60% decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK) phosphorylation and activation.
208	12176727	Insulin inhibition of MAPK was accompanied by a rapid induction of MAPK phosphatase (MKP-1), which inactivates MAPKs by dephosphorylation.
209	12176727	Pretreatment with inhibitors of the nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration.
210	12176727	In contrast, adenoviral infection of VSMCs with MKP-1 or cGMP-dependent protein kinase Ialpha (cGK Ialpha), the downstream effector of cGMP signaling, blocked the activation of MAPK and prevented PDGF-directed VSMC migration.
211	12176727	Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPK phosphorylation.
212	12176727	We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Ialpha induction of MKP-1 and consequent inactivation of MAPKs.
213	12176727	Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs.
214	12176727	Platelet-derived growth factor (PDGF) increased VSMC migration, which was inhibited by pretreatment with insulin in a dose-dependent manner.
215	12176727	Insulin also caused a 60% decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK) phosphorylation and activation.
216	12176727	Insulin inhibition of MAPK was accompanied by a rapid induction of MAPK phosphatase (MKP-1), which inactivates MAPKs by dephosphorylation.
217	12176727	Pretreatment with inhibitors of the nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration.
218	12176727	In contrast, adenoviral infection of VSMCs with MKP-1 or cGMP-dependent protein kinase Ialpha (cGK Ialpha), the downstream effector of cGMP signaling, blocked the activation of MAPK and prevented PDGF-directed VSMC migration.
219	12176727	Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPK phosphorylation.
220	12176727	We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Ialpha induction of MKP-1 and consequent inactivation of MAPKs.
221	14578290	Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells.
222	14578290	Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets.
223	14578290	We examined the mechanism of PTHrP-induced insulin expression.
224	14578290	The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP.
225	14578290	Because SB203580 inhibits both p38 and c-jun NH(2)-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125.
226	14578290	PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF.
227	14578290	We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2.
228	14578290	MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP.
229	14578290	PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1.
230	14578290	Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells.
231	14578290	The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity.
232	14578290	Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway.
233	14578290	Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells.
234	14578290	Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets.
235	14578290	We examined the mechanism of PTHrP-induced insulin expression.
236	14578290	The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP.
237	14578290	Because SB203580 inhibits both p38 and c-jun NH(2)-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125.
238	14578290	PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF.
239	14578290	We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2.
240	14578290	MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP.
241	14578290	PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1.
242	14578290	Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells.
243	14578290	The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity.
244	14578290	Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway.
245	14578290	Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells.
246	14578290	Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets.
247	14578290	We examined the mechanism of PTHrP-induced insulin expression.
248	14578290	The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP.
249	14578290	Because SB203580 inhibits both p38 and c-jun NH(2)-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125.
250	14578290	PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF.
251	14578290	We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2.
252	14578290	MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP.
253	14578290	PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1.
254	14578290	Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells.
255	14578290	The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity.
256	14578290	Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway.
257	14578290	Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells.
258	14578290	Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets.
259	14578290	We examined the mechanism of PTHrP-induced insulin expression.
260	14578290	The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP.
261	14578290	Because SB203580 inhibits both p38 and c-jun NH(2)-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125.
262	14578290	PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF.
263	14578290	We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2.
264	14578290	MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP.
265	14578290	PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1.
266	14578290	Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells.
267	14578290	The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity.
268	14578290	Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway.
269	15269202	Role of MAPK phosphatase-1 (MKP-1) in adipocyte differentiation.
270	15269202	We have now shown that the activity, but not the abundance, of p42/p44 mitogen-activated protein kinase (MAPK) is down-regulated during adipocyte differentiation.
271	15269202	This decrease in p42/p44 MAPK activity does not appear to be a direct effect of hormonal inducers of differentiation but rather represents a characteristic event of adipocyte differentiation that is achieved through a persistent change in intracellular signaling.
272	15269202	Although the phosphorylation or abundance of MEK, an upstream kinase for p42/p44 MAPK, was not altered during differentiation, the abundance of MAPK phosphatase-1 (MKP-1), a negative regulator of p42/p44 MAPK, was increased with a time course similar to that of the down-regulation of p42/p44 MAPK activity.
273	15269202	Ectopic expression of MKP-1 in preadipocytes reduced and depletion of endogenous MKP-1 in mature adipocytes increased the activity of p42/p44 MAPK.
274	15269202	Prevention of the up-regulation of MKP-1 abundance in preadipocytes by expression of Mkp-1 antisense RNA resulted in persistence of p42/p44 MAPK activation and blocked differentiation, effects that were reversed by the MEK inhibitor PD98059.
275	15269202	These results suggest that MKP-1 plays an essential role in adipocyte differentiation through down-regulation of p42/p44 MAPK activity.
276	15269202	Role of MAPK phosphatase-1 (MKP-1) in adipocyte differentiation.
277	15269202	We have now shown that the activity, but not the abundance, of p42/p44 mitogen-activated protein kinase (MAPK) is down-regulated during adipocyte differentiation.
278	15269202	This decrease in p42/p44 MAPK activity does not appear to be a direct effect of hormonal inducers of differentiation but rather represents a characteristic event of adipocyte differentiation that is achieved through a persistent change in intracellular signaling.
279	15269202	Although the phosphorylation or abundance of MEK, an upstream kinase for p42/p44 MAPK, was not altered during differentiation, the abundance of MAPK phosphatase-1 (MKP-1), a negative regulator of p42/p44 MAPK, was increased with a time course similar to that of the down-regulation of p42/p44 MAPK activity.
280	15269202	Ectopic expression of MKP-1 in preadipocytes reduced and depletion of endogenous MKP-1 in mature adipocytes increased the activity of p42/p44 MAPK.
281	15269202	Prevention of the up-regulation of MKP-1 abundance in preadipocytes by expression of Mkp-1 antisense RNA resulted in persistence of p42/p44 MAPK activation and blocked differentiation, effects that were reversed by the MEK inhibitor PD98059.
282	15269202	These results suggest that MKP-1 plays an essential role in adipocyte differentiation through down-regulation of p42/p44 MAPK activity.
283	15269202	Role of MAPK phosphatase-1 (MKP-1) in adipocyte differentiation.
284	15269202	We have now shown that the activity, but not the abundance, of p42/p44 mitogen-activated protein kinase (MAPK) is down-regulated during adipocyte differentiation.
285	15269202	This decrease in p42/p44 MAPK activity does not appear to be a direct effect of hormonal inducers of differentiation but rather represents a characteristic event of adipocyte differentiation that is achieved through a persistent change in intracellular signaling.
286	15269202	Although the phosphorylation or abundance of MEK, an upstream kinase for p42/p44 MAPK, was not altered during differentiation, the abundance of MAPK phosphatase-1 (MKP-1), a negative regulator of p42/p44 MAPK, was increased with a time course similar to that of the down-regulation of p42/p44 MAPK activity.
287	15269202	Ectopic expression of MKP-1 in preadipocytes reduced and depletion of endogenous MKP-1 in mature adipocytes increased the activity of p42/p44 MAPK.
288	15269202	Prevention of the up-regulation of MKP-1 abundance in preadipocytes by expression of Mkp-1 antisense RNA resulted in persistence of p42/p44 MAPK activation and blocked differentiation, effects that were reversed by the MEK inhibitor PD98059.
289	15269202	These results suggest that MKP-1 plays an essential role in adipocyte differentiation through down-regulation of p42/p44 MAPK activity.
290	15269202	Role of MAPK phosphatase-1 (MKP-1) in adipocyte differentiation.
291	15269202	We have now shown that the activity, but not the abundance, of p42/p44 mitogen-activated protein kinase (MAPK) is down-regulated during adipocyte differentiation.
292	15269202	This decrease in p42/p44 MAPK activity does not appear to be a direct effect of hormonal inducers of differentiation but rather represents a characteristic event of adipocyte differentiation that is achieved through a persistent change in intracellular signaling.
293	15269202	Although the phosphorylation or abundance of MEK, an upstream kinase for p42/p44 MAPK, was not altered during differentiation, the abundance of MAPK phosphatase-1 (MKP-1), a negative regulator of p42/p44 MAPK, was increased with a time course similar to that of the down-regulation of p42/p44 MAPK activity.
294	15269202	Ectopic expression of MKP-1 in preadipocytes reduced and depletion of endogenous MKP-1 in mature adipocytes increased the activity of p42/p44 MAPK.
295	15269202	Prevention of the up-regulation of MKP-1 abundance in preadipocytes by expression of Mkp-1 antisense RNA resulted in persistence of p42/p44 MAPK activation and blocked differentiation, effects that were reversed by the MEK inhibitor PD98059.
296	15269202	These results suggest that MKP-1 plays an essential role in adipocyte differentiation through down-regulation of p42/p44 MAPK activity.
297	15269202	Role of MAPK phosphatase-1 (MKP-1) in adipocyte differentiation.
298	15269202	We have now shown that the activity, but not the abundance, of p42/p44 mitogen-activated protein kinase (MAPK) is down-regulated during adipocyte differentiation.
299	15269202	This decrease in p42/p44 MAPK activity does not appear to be a direct effect of hormonal inducers of differentiation but rather represents a characteristic event of adipocyte differentiation that is achieved through a persistent change in intracellular signaling.
300	15269202	Although the phosphorylation or abundance of MEK, an upstream kinase for p42/p44 MAPK, was not altered during differentiation, the abundance of MAPK phosphatase-1 (MKP-1), a negative regulator of p42/p44 MAPK, was increased with a time course similar to that of the down-regulation of p42/p44 MAPK activity.
301	15269202	Ectopic expression of MKP-1 in preadipocytes reduced and depletion of endogenous MKP-1 in mature adipocytes increased the activity of p42/p44 MAPK.
302	15269202	Prevention of the up-regulation of MKP-1 abundance in preadipocytes by expression of Mkp-1 antisense RNA resulted in persistence of p42/p44 MAPK activation and blocked differentiation, effects that were reversed by the MEK inhibitor PD98059.
303	15269202	These results suggest that MKP-1 plays an essential role in adipocyte differentiation through down-regulation of p42/p44 MAPK activity.
304	15355857	In normal WKY VSMC, insulin increased MAPK phosphatase-1 (MKP-1) expression as well as MKP-1 phosphorylation, which stabilizes it, and inhibited PDGF-mediated MAPK phosphorylation and cell migration.
305	15355857	In contrast, basal migration was elevated in GK diabetic VSMCs, and all of insulin's effects on MKP-1 expression and phosphorylation, MAPK phosphorylation, and PDGF-stimulated migration were markedly inhibited.
306	15355857	The critical importance of MKP-1 in insulin inhibition of VSMC migration was evident from several observations.
307	15355857	MKP-1 small interfering RNA inhibited MKP-1 expression and abolished insulin inhibition of PDGF-induced VSMC migration.
308	15355857	Conversely, adenoviral expression of MKP-1 decreased MAPK phosphorylation and basal migration rate and restored insulin's ability to inhibit PDGF-directed migration in GK diabetic VSMCs.
309	15355857	Adenoviral expression of cGK Ialpha enhanced MKP-1 inhibition of MAPK phosphorylation and VSMC migration.
310	15355857	We conclude that enhanced VSMC migration in GK diabetic rats is due at least in part to a failure of insulin-stimulated cGMP/cGK Ialpha signaling, MKP-1 expression, and stabilization and thus MAPK inactivation.
311	15355857	In normal WKY VSMC, insulin increased MAPK phosphatase-1 (MKP-1) expression as well as MKP-1 phosphorylation, which stabilizes it, and inhibited PDGF-mediated MAPK phosphorylation and cell migration.
312	15355857	In contrast, basal migration was elevated in GK diabetic VSMCs, and all of insulin's effects on MKP-1 expression and phosphorylation, MAPK phosphorylation, and PDGF-stimulated migration were markedly inhibited.
313	15355857	The critical importance of MKP-1 in insulin inhibition of VSMC migration was evident from several observations.
314	15355857	MKP-1 small interfering RNA inhibited MKP-1 expression and abolished insulin inhibition of PDGF-induced VSMC migration.
315	15355857	Conversely, adenoviral expression of MKP-1 decreased MAPK phosphorylation and basal migration rate and restored insulin's ability to inhibit PDGF-directed migration in GK diabetic VSMCs.
316	15355857	Adenoviral expression of cGK Ialpha enhanced MKP-1 inhibition of MAPK phosphorylation and VSMC migration.
317	15355857	We conclude that enhanced VSMC migration in GK diabetic rats is due at least in part to a failure of insulin-stimulated cGMP/cGK Ialpha signaling, MKP-1 expression, and stabilization and thus MAPK inactivation.
318	15355857	In normal WKY VSMC, insulin increased MAPK phosphatase-1 (MKP-1) expression as well as MKP-1 phosphorylation, which stabilizes it, and inhibited PDGF-mediated MAPK phosphorylation and cell migration.
319	15355857	In contrast, basal migration was elevated in GK diabetic VSMCs, and all of insulin's effects on MKP-1 expression and phosphorylation, MAPK phosphorylation, and PDGF-stimulated migration were markedly inhibited.
320	15355857	The critical importance of MKP-1 in insulin inhibition of VSMC migration was evident from several observations.
321	15355857	MKP-1 small interfering RNA inhibited MKP-1 expression and abolished insulin inhibition of PDGF-induced VSMC migration.
322	15355857	Conversely, adenoviral expression of MKP-1 decreased MAPK phosphorylation and basal migration rate and restored insulin's ability to inhibit PDGF-directed migration in GK diabetic VSMCs.
323	15355857	Adenoviral expression of cGK Ialpha enhanced MKP-1 inhibition of MAPK phosphorylation and VSMC migration.
324	15355857	We conclude that enhanced VSMC migration in GK diabetic rats is due at least in part to a failure of insulin-stimulated cGMP/cGK Ialpha signaling, MKP-1 expression, and stabilization and thus MAPK inactivation.
325	15355857	In normal WKY VSMC, insulin increased MAPK phosphatase-1 (MKP-1) expression as well as MKP-1 phosphorylation, which stabilizes it, and inhibited PDGF-mediated MAPK phosphorylation and cell migration.
326	15355857	In contrast, basal migration was elevated in GK diabetic VSMCs, and all of insulin's effects on MKP-1 expression and phosphorylation, MAPK phosphorylation, and PDGF-stimulated migration were markedly inhibited.
327	15355857	The critical importance of MKP-1 in insulin inhibition of VSMC migration was evident from several observations.
328	15355857	MKP-1 small interfering RNA inhibited MKP-1 expression and abolished insulin inhibition of PDGF-induced VSMC migration.
329	15355857	Conversely, adenoviral expression of MKP-1 decreased MAPK phosphorylation and basal migration rate and restored insulin's ability to inhibit PDGF-directed migration in GK diabetic VSMCs.
330	15355857	Adenoviral expression of cGK Ialpha enhanced MKP-1 inhibition of MAPK phosphorylation and VSMC migration.
331	15355857	We conclude that enhanced VSMC migration in GK diabetic rats is due at least in part to a failure of insulin-stimulated cGMP/cGK Ialpha signaling, MKP-1 expression, and stabilization and thus MAPK inactivation.
332	15355857	In normal WKY VSMC, insulin increased MAPK phosphatase-1 (MKP-1) expression as well as MKP-1 phosphorylation, which stabilizes it, and inhibited PDGF-mediated MAPK phosphorylation and cell migration.
333	15355857	In contrast, basal migration was elevated in GK diabetic VSMCs, and all of insulin's effects on MKP-1 expression and phosphorylation, MAPK phosphorylation, and PDGF-stimulated migration were markedly inhibited.
334	15355857	The critical importance of MKP-1 in insulin inhibition of VSMC migration was evident from several observations.
335	15355857	MKP-1 small interfering RNA inhibited MKP-1 expression and abolished insulin inhibition of PDGF-induced VSMC migration.
336	15355857	Conversely, adenoviral expression of MKP-1 decreased MAPK phosphorylation and basal migration rate and restored insulin's ability to inhibit PDGF-directed migration in GK diabetic VSMCs.
337	15355857	Adenoviral expression of cGK Ialpha enhanced MKP-1 inhibition of MAPK phosphorylation and VSMC migration.
338	15355857	We conclude that enhanced VSMC migration in GK diabetic rats is due at least in part to a failure of insulin-stimulated cGMP/cGK Ialpha signaling, MKP-1 expression, and stabilization and thus MAPK inactivation.
339	15355857	In normal WKY VSMC, insulin increased MAPK phosphatase-1 (MKP-1) expression as well as MKP-1 phosphorylation, which stabilizes it, and inhibited PDGF-mediated MAPK phosphorylation and cell migration.
340	15355857	In contrast, basal migration was elevated in GK diabetic VSMCs, and all of insulin's effects on MKP-1 expression and phosphorylation, MAPK phosphorylation, and PDGF-stimulated migration were markedly inhibited.
341	15355857	The critical importance of MKP-1 in insulin inhibition of VSMC migration was evident from several observations.
342	15355857	MKP-1 small interfering RNA inhibited MKP-1 expression and abolished insulin inhibition of PDGF-induced VSMC migration.
343	15355857	Conversely, adenoviral expression of MKP-1 decreased MAPK phosphorylation and basal migration rate and restored insulin's ability to inhibit PDGF-directed migration in GK diabetic VSMCs.
344	15355857	Adenoviral expression of cGK Ialpha enhanced MKP-1 inhibition of MAPK phosphorylation and VSMC migration.
345	15355857	We conclude that enhanced VSMC migration in GK diabetic rats is due at least in part to a failure of insulin-stimulated cGMP/cGK Ialpha signaling, MKP-1 expression, and stabilization and thus MAPK inactivation.
346	15355857	In normal WKY VSMC, insulin increased MAPK phosphatase-1 (MKP-1) expression as well as MKP-1 phosphorylation, which stabilizes it, and inhibited PDGF-mediated MAPK phosphorylation and cell migration.
347	15355857	In contrast, basal migration was elevated in GK diabetic VSMCs, and all of insulin's effects on MKP-1 expression and phosphorylation, MAPK phosphorylation, and PDGF-stimulated migration were markedly inhibited.
348	15355857	The critical importance of MKP-1 in insulin inhibition of VSMC migration was evident from several observations.
349	15355857	MKP-1 small interfering RNA inhibited MKP-1 expression and abolished insulin inhibition of PDGF-induced VSMC migration.
350	15355857	Conversely, adenoviral expression of MKP-1 decreased MAPK phosphorylation and basal migration rate and restored insulin's ability to inhibit PDGF-directed migration in GK diabetic VSMCs.
351	15355857	Adenoviral expression of cGK Ialpha enhanced MKP-1 inhibition of MAPK phosphorylation and VSMC migration.
352	15355857	We conclude that enhanced VSMC migration in GK diabetic rats is due at least in part to a failure of insulin-stimulated cGMP/cGK Ialpha signaling, MKP-1 expression, and stabilization and thus MAPK inactivation.
353	15793232	Real-time PCR corroborated the induction of six genes (angiotensinogen, GLUT-1, inhibitor of kappaB, inhibitor of DNA binding 1 [ID-1], Ubp41, and mitogen-activated protein kinase phosphatase-1 [MKP-1]) by insulin-induced hypoglycemia in the hypothalamus: five of these six genes in cortex and three (GLUT-1, angiotensinogen, and MKP-1) in liver.
354	15793232	Four of these genes (angiotensinogen, GLUT-1, ID-1, and MKP-1) have been implicated in enhancement of glucose availability, which could plausibly serve a neuroprotective role during acute hypoglycemia but, if persistent, could also cause glucose-sensing mechanisms to overestimate plasma glucose levels, potentially causing hypoglycemia-induced counterregulatory failure.
355	15793232	Real-time PCR corroborated the induction of six genes (angiotensinogen, GLUT-1, inhibitor of kappaB, inhibitor of DNA binding 1 [ID-1], Ubp41, and mitogen-activated protein kinase phosphatase-1 [MKP-1]) by insulin-induced hypoglycemia in the hypothalamus: five of these six genes in cortex and three (GLUT-1, angiotensinogen, and MKP-1) in liver.
356	15793232	Four of these genes (angiotensinogen, GLUT-1, ID-1, and MKP-1) have been implicated in enhancement of glucose availability, which could plausibly serve a neuroprotective role during acute hypoglycemia but, if persistent, could also cause glucose-sensing mechanisms to overestimate plasma glucose levels, potentially causing hypoglycemia-induced counterregulatory failure.
357	16814733	Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity.
358	16814733	Here we show that mice lacking the nuclear-localized MKP, MKP-1 (mkp-1(-/-)), have enhanced Erk, p38 MAPK and c-Jun NH(2)-terminal kinase (JNK) activities in insulin-responsive tissues as compared with wild-type mice.
359	16814733	Although JNK promotes insulin resistance, mkp-1(-/-) mice exhibited unimpaired insulin-mediated signaling and glucose homeostasis.
360	16814733	We reconciled these results by demonstrating that in mkp-1(-/-) mice, JNK activity was increased in the nucleus, but not the cytosol.
361	16814733	These results suggest that nuclear regulation of the MAPKs by MKP-1 is essential for the management of metabolic homeostasis in a manner that is spatially uncoupled from the cytosolic actions of the MAPKs.
362	16814733	Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity.
363	16814733	Here we show that mice lacking the nuclear-localized MKP, MKP-1 (mkp-1(-/-)), have enhanced Erk, p38 MAPK and c-Jun NH(2)-terminal kinase (JNK) activities in insulin-responsive tissues as compared with wild-type mice.
364	16814733	Although JNK promotes insulin resistance, mkp-1(-/-) mice exhibited unimpaired insulin-mediated signaling and glucose homeostasis.
365	16814733	We reconciled these results by demonstrating that in mkp-1(-/-) mice, JNK activity was increased in the nucleus, but not the cytosol.
366	16814733	These results suggest that nuclear regulation of the MAPKs by MKP-1 is essential for the management of metabolic homeostasis in a manner that is spatially uncoupled from the cytosolic actions of the MAPKs.
367	16814733	Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity.
368	16814733	Here we show that mice lacking the nuclear-localized MKP, MKP-1 (mkp-1(-/-)), have enhanced Erk, p38 MAPK and c-Jun NH(2)-terminal kinase (JNK) activities in insulin-responsive tissues as compared with wild-type mice.
369	16814733	Although JNK promotes insulin resistance, mkp-1(-/-) mice exhibited unimpaired insulin-mediated signaling and glucose homeostasis.
370	16814733	We reconciled these results by demonstrating that in mkp-1(-/-) mice, JNK activity was increased in the nucleus, but not the cytosol.
371	16814733	These results suggest that nuclear regulation of the MAPKs by MKP-1 is essential for the management of metabolic homeostasis in a manner that is spatially uncoupled from the cytosolic actions of the MAPKs.
372	16814733	Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity.
373	16814733	Here we show that mice lacking the nuclear-localized MKP, MKP-1 (mkp-1(-/-)), have enhanced Erk, p38 MAPK and c-Jun NH(2)-terminal kinase (JNK) activities in insulin-responsive tissues as compared with wild-type mice.
374	16814733	Although JNK promotes insulin resistance, mkp-1(-/-) mice exhibited unimpaired insulin-mediated signaling and glucose homeostasis.
375	16814733	We reconciled these results by demonstrating that in mkp-1(-/-) mice, JNK activity was increased in the nucleus, but not the cytosol.
376	16814733	These results suggest that nuclear regulation of the MAPKs by MKP-1 is essential for the management of metabolic homeostasis in a manner that is spatially uncoupled from the cytosolic actions of the MAPKs.
377	16919785	Many PTPs are recognized as potential drug targets; however, inhibitor development has focused only on a small number of enzymes, most notably PTP1B for type II diabetes and obesity, and MKP1 and CDC25 for cancer.
378	16919785	In this article, we focus on the family of mitogen-activated protein kinase (MAPK)-specific tyrosine phosphatases--PTPN5 [also called striatal-enriched phosphatase (STEP)], PTPN7 (also called hematopoietic PTP) and PTPRR (also called PC12 PTP or STEP-like PTP)--and discuss approaches for achieving selectivity for the MAPK-PTPs at the molecular level using recently determined high-resolution X-ray crystal structures.
379	17063547	[Effects of pioglitazone on MKP-1 and TSP-1 expression in early stages of diabetic retinopathy induced by streptozotocin].
380	17401436	Renal p38 MAP kinase activity in experimental diabetes.
381	17401436	We examined the p38 pathway in renal cortex of rats with streptozotocin diabetes (4 weeks) with poor (DS), moderate (DM), and intensive (DII) metabolic control, achieved by varying doses of insulin therapy.
382	17401436	Renal p38 was also studied in 12-month diabetic rats with established nephropathy (DM12) and compared with age-matched controls. p38 activity (in vitro kinase assay and expression of phosphorylated (active) p38 (P-p38)) was increased in DM and DS rats, as compared with non-diabetic controls, and attenuated by intensive insulin treatment.
383	17401436	Enhanced p38 activity in DS and DM rats was not associated with increases in expression of active mitogen-activated protein kinase 3/6, an activator of p38, but paralleled with increased expression of scaffolding protein transforming growth factor-beta-activated protein kinase 1-binding protein 1.
384	17401436	Expression of mitogen-activated protein phosphatase-1 (MKP-1), one of the phosphatases involved in inactivation of mitogen-activated protein kinase signaling, was increased in all diabetic groups, irrespective of metabolic control.
385	17401436	In summary, renal cortical p38 activity was increased in diabetic rats at early and advanced stages of nephropathy, as compared with non-diabetic animals, and attenuated by improved metabolic control. p38 activation in diabetes is likely to occur via multiple pathways and cannot be explained by downregulation of MKP-1.
386	17401436	Renal p38 MAP kinase activity in experimental diabetes.
387	17401436	We examined the p38 pathway in renal cortex of rats with streptozotocin diabetes (4 weeks) with poor (DS), moderate (DM), and intensive (DII) metabolic control, achieved by varying doses of insulin therapy.
388	17401436	Renal p38 was also studied in 12-month diabetic rats with established nephropathy (DM12) and compared with age-matched controls. p38 activity (in vitro kinase assay and expression of phosphorylated (active) p38 (P-p38)) was increased in DM and DS rats, as compared with non-diabetic controls, and attenuated by intensive insulin treatment.
389	17401436	Enhanced p38 activity in DS and DM rats was not associated with increases in expression of active mitogen-activated protein kinase 3/6, an activator of p38, but paralleled with increased expression of scaffolding protein transforming growth factor-beta-activated protein kinase 1-binding protein 1.
390	17401436	Expression of mitogen-activated protein phosphatase-1 (MKP-1), one of the phosphatases involved in inactivation of mitogen-activated protein kinase signaling, was increased in all diabetic groups, irrespective of metabolic control.
391	17401436	In summary, renal cortical p38 activity was increased in diabetic rats at early and advanced stages of nephropathy, as compared with non-diabetic animals, and attenuated by improved metabolic control. p38 activation in diabetes is likely to occur via multiple pathways and cannot be explained by downregulation of MKP-1.
392	17601561	Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats.
393	17601561	We determined the expression level of growth-associated protein-43 (GAP-43) and mitogen activated protein kinase phosphatase-1 (MKP-1) in the hippocampus by immunohistochemistry.
394	17601561	The optical density as well as the positive neuron number for GAP-43 and MKP-1 decreased significantly in the CA1 and DG Hippocampal area in diabetic rats (P<0.01).
395	17601561	These results indicated that DM could down-regulate GAP-43 and MKP-1 expression in Hippocampal area that is in charge of memory and cognition.
396	17601561	As indicated by our study, the changes in GAP-43 and MKP-1 expression in hippocampus may play a role in the pathogenesis of diabetic dementia.
397	17601561	Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats.
398	17601561	We determined the expression level of growth-associated protein-43 (GAP-43) and mitogen activated protein kinase phosphatase-1 (MKP-1) in the hippocampus by immunohistochemistry.
399	17601561	The optical density as well as the positive neuron number for GAP-43 and MKP-1 decreased significantly in the CA1 and DG Hippocampal area in diabetic rats (P<0.01).
400	17601561	These results indicated that DM could down-regulate GAP-43 and MKP-1 expression in Hippocampal area that is in charge of memory and cognition.
401	17601561	As indicated by our study, the changes in GAP-43 and MKP-1 expression in hippocampus may play a role in the pathogenesis of diabetic dementia.
402	17601561	Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats.
403	17601561	We determined the expression level of growth-associated protein-43 (GAP-43) and mitogen activated protein kinase phosphatase-1 (MKP-1) in the hippocampus by immunohistochemistry.
404	17601561	The optical density as well as the positive neuron number for GAP-43 and MKP-1 decreased significantly in the CA1 and DG Hippocampal area in diabetic rats (P<0.01).
405	17601561	These results indicated that DM could down-regulate GAP-43 and MKP-1 expression in Hippocampal area that is in charge of memory and cognition.
406	17601561	As indicated by our study, the changes in GAP-43 and MKP-1 expression in hippocampus may play a role in the pathogenesis of diabetic dementia.
407	17601561	Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats.
408	17601561	We determined the expression level of growth-associated protein-43 (GAP-43) and mitogen activated protein kinase phosphatase-1 (MKP-1) in the hippocampus by immunohistochemistry.
409	17601561	The optical density as well as the positive neuron number for GAP-43 and MKP-1 decreased significantly in the CA1 and DG Hippocampal area in diabetic rats (P<0.01).
410	17601561	These results indicated that DM could down-regulate GAP-43 and MKP-1 expression in Hippocampal area that is in charge of memory and cognition.
411	17601561	As indicated by our study, the changes in GAP-43 and MKP-1 expression in hippocampus may play a role in the pathogenesis of diabetic dementia.
412	17601561	Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats.
413	17601561	We determined the expression level of growth-associated protein-43 (GAP-43) and mitogen activated protein kinase phosphatase-1 (MKP-1) in the hippocampus by immunohistochemistry.
414	17601561	The optical density as well as the positive neuron number for GAP-43 and MKP-1 decreased significantly in the CA1 and DG Hippocampal area in diabetic rats (P<0.01).
415	17601561	These results indicated that DM could down-regulate GAP-43 and MKP-1 expression in Hippocampal area that is in charge of memory and cognition.
416	17601561	As indicated by our study, the changes in GAP-43 and MKP-1 expression in hippocampus may play a role in the pathogenesis of diabetic dementia.
417	17647144	Expression changes of mitogen-activated protein kinase phosphatase-1 (MKP-1) in myocardium of streptozotocin-induced diabetic rats.
418	17647144	MAP Kinase Phosphatase-1 (MKP-1) is a dual specific phosphatase selective for MAP kinases, and was believed to implicate in the development of cardiac hypertrophy.
419	17647144	Moreover, we provided first evidence that down-regulation of cardioprotective peptide MKP-1, the MAPK pathway negative regulator, in myocardium of streptozotocin-induced diabetic rats, which may contribute to the deterioration of cardiac function and lead to diabetic cardiomyopathy.
420	17647144	Expression changes of mitogen-activated protein kinase phosphatase-1 (MKP-1) in myocardium of streptozotocin-induced diabetic rats.
421	17647144	MAP Kinase Phosphatase-1 (MKP-1) is a dual specific phosphatase selective for MAP kinases, and was believed to implicate in the development of cardiac hypertrophy.
422	17647144	Moreover, we provided first evidence that down-regulation of cardioprotective peptide MKP-1, the MAPK pathway negative regulator, in myocardium of streptozotocin-induced diabetic rats, which may contribute to the deterioration of cardiac function and lead to diabetic cardiomyopathy.
423	17647144	Expression changes of mitogen-activated protein kinase phosphatase-1 (MKP-1) in myocardium of streptozotocin-induced diabetic rats.
424	17647144	MAP Kinase Phosphatase-1 (MKP-1) is a dual specific phosphatase selective for MAP kinases, and was believed to implicate in the development of cardiac hypertrophy.
425	17647144	Moreover, we provided first evidence that down-regulation of cardioprotective peptide MKP-1, the MAPK pathway negative regulator, in myocardium of streptozotocin-induced diabetic rats, which may contribute to the deterioration of cardiac function and lead to diabetic cardiomyopathy.
426	18855677	We present herein an overview of the progress, along with a brief description of applications to two types of DSPs: Cdc25 and MAP kinase phosphatase (MKP) family members.
427	18855677	In particular, we focus on combined computational and experimental efforts for designing Cdc25B and MKP-1 inhibitors and understanding their mechanisms of interactions with their target proteins.
428	21562305	Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway.
429	21562305	The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα-/- myocytes and in XCT790-treated C2C12.
430	21562305	The ERRα-PGC-1α complex activates the Dusp1 gene, which encodes MKP-1, and ERRα occupies the proximal 5' regulatory region during early differentiation in C2C12 myocytes.
431	21562305	Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling.
432	21562305	Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway.
433	21562305	The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα-/- myocytes and in XCT790-treated C2C12.
434	21562305	The ERRα-PGC-1α complex activates the Dusp1 gene, which encodes MKP-1, and ERRα occupies the proximal 5' regulatory region during early differentiation in C2C12 myocytes.
435	21562305	Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling.
436	22068113	Early intensive insulin therapy attenuates the p38 pathway in the renal cortex and indices of nephropathy in diabetic rats.
437	22068113	Activities of MKK3/6, CREB and MKP-1 proteins as well as CREB and MKP-1 mRNA showed a similar pattern.
438	22068113	However, late insulin therapy did not abrogate the increased renal cortical p38 MAPK pathway activation in diabetic rats and led to glomerular hypertrophy and extracellular matrix expansion.
439	22415879	Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1.
440	22415879	Mitochondrial contents, expression, and activation status of p38 mitogen-activated protein kinase (MAPK) and PPARγ coactivator 1α (PGC-1α) were compared between skeletal muscle samples from adiponectin gene knockout, adiponectin-reconstituted, and control mice.
441	22415879	Adenovirus-mediated adiponectin and MAPK phosphatase-1 (MKP1) overexpression were used to verify the relationship of MKP1 and PGC-1α in adiponectin-enhanced mitochondrial biogenesis using cultured C2C12 myotubes and PGC-1α knockout mice.
442	22415879	An inhibitory effect of adiponectin on MKP1 gene expression was observed in mouse skeletal muscle and cultured C2C12 myotubes.
443	22415879	Overexpression of MKP1 attenuated adiponectin-enhanced mitochondrial biogenesis, with significantly decreased PGC-1α expression and p38 MAPK phosphorylation.
444	22415879	Although in vivo adiponectin overexpression reduced MKP1 protein levels, the stimulative effects of adiponectin on mitochondrial biogenesis vanished in skeletal muscle of PGC-1α knockout mice.
445	22415879	Therefore, our study indicates that adiponectin enhances p38 MAPK/PGC-1α signaling and mitochondrial biogenesis in skeletal muscle by suppressing MKP1 expression.
446	22415879	Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1.
447	22415879	Mitochondrial contents, expression, and activation status of p38 mitogen-activated protein kinase (MAPK) and PPARγ coactivator 1α (PGC-1α) were compared between skeletal muscle samples from adiponectin gene knockout, adiponectin-reconstituted, and control mice.
448	22415879	Adenovirus-mediated adiponectin and MAPK phosphatase-1 (MKP1) overexpression were used to verify the relationship of MKP1 and PGC-1α in adiponectin-enhanced mitochondrial biogenesis using cultured C2C12 myotubes and PGC-1α knockout mice.
449	22415879	An inhibitory effect of adiponectin on MKP1 gene expression was observed in mouse skeletal muscle and cultured C2C12 myotubes.
450	22415879	Overexpression of MKP1 attenuated adiponectin-enhanced mitochondrial biogenesis, with significantly decreased PGC-1α expression and p38 MAPK phosphorylation.
451	22415879	Although in vivo adiponectin overexpression reduced MKP1 protein levels, the stimulative effects of adiponectin on mitochondrial biogenesis vanished in skeletal muscle of PGC-1α knockout mice.
452	22415879	Therefore, our study indicates that adiponectin enhances p38 MAPK/PGC-1α signaling and mitochondrial biogenesis in skeletal muscle by suppressing MKP1 expression.
453	22415879	Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1.
454	22415879	Mitochondrial contents, expression, and activation status of p38 mitogen-activated protein kinase (MAPK) and PPARγ coactivator 1α (PGC-1α) were compared between skeletal muscle samples from adiponectin gene knockout, adiponectin-reconstituted, and control mice.
455	22415879	Adenovirus-mediated adiponectin and MAPK phosphatase-1 (MKP1) overexpression were used to verify the relationship of MKP1 and PGC-1α in adiponectin-enhanced mitochondrial biogenesis using cultured C2C12 myotubes and PGC-1α knockout mice.
456	22415879	An inhibitory effect of adiponectin on MKP1 gene expression was observed in mouse skeletal muscle and cultured C2C12 myotubes.
457	22415879	Overexpression of MKP1 attenuated adiponectin-enhanced mitochondrial biogenesis, with significantly decreased PGC-1α expression and p38 MAPK phosphorylation.
458	22415879	Although in vivo adiponectin overexpression reduced MKP1 protein levels, the stimulative effects of adiponectin on mitochondrial biogenesis vanished in skeletal muscle of PGC-1α knockout mice.
459	22415879	Therefore, our study indicates that adiponectin enhances p38 MAPK/PGC-1α signaling and mitochondrial biogenesis in skeletal muscle by suppressing MKP1 expression.
460	22415879	Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1.
461	22415879	Mitochondrial contents, expression, and activation status of p38 mitogen-activated protein kinase (MAPK) and PPARγ coactivator 1α (PGC-1α) were compared between skeletal muscle samples from adiponectin gene knockout, adiponectin-reconstituted, and control mice.
462	22415879	Adenovirus-mediated adiponectin and MAPK phosphatase-1 (MKP1) overexpression were used to verify the relationship of MKP1 and PGC-1α in adiponectin-enhanced mitochondrial biogenesis using cultured C2C12 myotubes and PGC-1α knockout mice.
463	22415879	An inhibitory effect of adiponectin on MKP1 gene expression was observed in mouse skeletal muscle and cultured C2C12 myotubes.
464	22415879	Overexpression of MKP1 attenuated adiponectin-enhanced mitochondrial biogenesis, with significantly decreased PGC-1α expression and p38 MAPK phosphorylation.
465	22415879	Although in vivo adiponectin overexpression reduced MKP1 protein levels, the stimulative effects of adiponectin on mitochondrial biogenesis vanished in skeletal muscle of PGC-1α knockout mice.
466	22415879	Therefore, our study indicates that adiponectin enhances p38 MAPK/PGC-1α signaling and mitochondrial biogenesis in skeletal muscle by suppressing MKP1 expression.
467	22415879	Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1.
468	22415879	Mitochondrial contents, expression, and activation status of p38 mitogen-activated protein kinase (MAPK) and PPARγ coactivator 1α (PGC-1α) were compared between skeletal muscle samples from adiponectin gene knockout, adiponectin-reconstituted, and control mice.
469	22415879	Adenovirus-mediated adiponectin and MAPK phosphatase-1 (MKP1) overexpression were used to verify the relationship of MKP1 and PGC-1α in adiponectin-enhanced mitochondrial biogenesis using cultured C2C12 myotubes and PGC-1α knockout mice.
470	22415879	An inhibitory effect of adiponectin on MKP1 gene expression was observed in mouse skeletal muscle and cultured C2C12 myotubes.
471	22415879	Overexpression of MKP1 attenuated adiponectin-enhanced mitochondrial biogenesis, with significantly decreased PGC-1α expression and p38 MAPK phosphorylation.
472	22415879	Although in vivo adiponectin overexpression reduced MKP1 protein levels, the stimulative effects of adiponectin on mitochondrial biogenesis vanished in skeletal muscle of PGC-1α knockout mice.
473	22415879	Therefore, our study indicates that adiponectin enhances p38 MAPK/PGC-1α signaling and mitochondrial biogenesis in skeletal muscle by suppressing MKP1 expression.
474	22991462	Redox regulation of MAPK phosphatase 1 controls monocyte migration and macrophage recruitment.
475	22991462	Chronic exposure of human THP-1 monocytes to diabetic conditions resulted in the loss of MKP-1 protein levels, the hyperactivation of ERK and p38 in response to monocyte chemoattractant protein-1 (MCP-1), and increased monocyte adhesion and chemotaxis.
476	22991462	Knockdown of MKP-1 mimicked the priming effects of metabolic stress, whereas MKP-1 overexpression blunted both MAPK activation and monocyte adhesion and migration induced by MCP-1.
477	22991462	Preventing MKP-1 S-glutathionylation in metabolically stressed monocytes by overexpressing glutaredoxin 1 protected MKP-1 from degradation and normalized monocyte adhesion and chemotaxis in response to MCP-1.
478	22991462	Redox regulation of MAPK phosphatase 1 controls monocyte migration and macrophage recruitment.
479	22991462	Chronic exposure of human THP-1 monocytes to diabetic conditions resulted in the loss of MKP-1 protein levels, the hyperactivation of ERK and p38 in response to monocyte chemoattractant protein-1 (MCP-1), and increased monocyte adhesion and chemotaxis.
480	22991462	Knockdown of MKP-1 mimicked the priming effects of metabolic stress, whereas MKP-1 overexpression blunted both MAPK activation and monocyte adhesion and migration induced by MCP-1.
481	22991462	Preventing MKP-1 S-glutathionylation in metabolically stressed monocytes by overexpressing glutaredoxin 1 protected MKP-1 from degradation and normalized monocyte adhesion and chemotaxis in response to MCP-1.
482	22991462	Redox regulation of MAPK phosphatase 1 controls monocyte migration and macrophage recruitment.
483	22991462	Chronic exposure of human THP-1 monocytes to diabetic conditions resulted in the loss of MKP-1 protein levels, the hyperactivation of ERK and p38 in response to monocyte chemoattractant protein-1 (MCP-1), and increased monocyte adhesion and chemotaxis.
484	22991462	Knockdown of MKP-1 mimicked the priming effects of metabolic stress, whereas MKP-1 overexpression blunted both MAPK activation and monocyte adhesion and migration induced by MCP-1.
485	22991462	Preventing MKP-1 S-glutathionylation in metabolically stressed monocytes by overexpressing glutaredoxin 1 protected MKP-1 from degradation and normalized monocyte adhesion and chemotaxis in response to MCP-1.
486	23056550	Regulation of the CCL2 gene in pancreatic β-cells by IL-1β and glucocorticoids: role of MKP-1.
487	23056550	Therefore, we investigated the positive and negative regulatory components controlling expression of the CCL2 gene using isolated rat islets and INS-1-derived β-cell lines.
488	23056550	We discovered that activation of the CCL2 gene by IL-1β required the p65 subunit of NF-κB and was dependent on genomic response elements located in the -3.6 kb region of the proximal gene promoter.
489	23056550	CCL2 gene transcription in response to IL-1β was blocked by pharmacological inhibition of the IKKβ and p38 MAPK pathways.
490	23056550	The IL-1β-mediated increase in CCL2 secretion was also impaired by p38 MAPK inhibition and by glucocorticoids.
491	23056550	Moreover, multiple synthetic glucocorticoids inhibited the IL-1β-stimulated induction of the CCL2 gene.
492	23056550	Induction of the MAP Kinase Phosphatase-1 (MKP-1) gene by glucocorticoids or by adenoviral-mediated overexpression decreased p38 MAPK phosphorylation, which diminished CCL2 gene expression, promoter activity, and release of CCL2 protein.
493	23056550	We conclude that glucocorticoid-mediated repression of IL-1β-induced CCL2 gene transcription and protein secretion occurs in part through the upregulation of the MKP-1 gene and subsequent deactivation of the p38 MAPK.
494	23056550	Furthermore, the anti-inflammatory actions observed with MKP-1 overexpression were obtained without suppressing glucose-stimulated insulin secretion.
495	23056550	Regulation of the CCL2 gene in pancreatic β-cells by IL-1β and glucocorticoids: role of MKP-1.
496	23056550	Therefore, we investigated the positive and negative regulatory components controlling expression of the CCL2 gene using isolated rat islets and INS-1-derived β-cell lines.
497	23056550	We discovered that activation of the CCL2 gene by IL-1β required the p65 subunit of NF-κB and was dependent on genomic response elements located in the -3.6 kb region of the proximal gene promoter.
498	23056550	CCL2 gene transcription in response to IL-1β was blocked by pharmacological inhibition of the IKKβ and p38 MAPK pathways.
499	23056550	The IL-1β-mediated increase in CCL2 secretion was also impaired by p38 MAPK inhibition and by glucocorticoids.
500	23056550	Moreover, multiple synthetic glucocorticoids inhibited the IL-1β-stimulated induction of the CCL2 gene.
501	23056550	Induction of the MAP Kinase Phosphatase-1 (MKP-1) gene by glucocorticoids or by adenoviral-mediated overexpression decreased p38 MAPK phosphorylation, which diminished CCL2 gene expression, promoter activity, and release of CCL2 protein.
502	23056550	We conclude that glucocorticoid-mediated repression of IL-1β-induced CCL2 gene transcription and protein secretion occurs in part through the upregulation of the MKP-1 gene and subsequent deactivation of the p38 MAPK.
503	23056550	Furthermore, the anti-inflammatory actions observed with MKP-1 overexpression were obtained without suppressing glucose-stimulated insulin secretion.
504	23056550	Regulation of the CCL2 gene in pancreatic β-cells by IL-1β and glucocorticoids: role of MKP-1.
505	23056550	Therefore, we investigated the positive and negative regulatory components controlling expression of the CCL2 gene using isolated rat islets and INS-1-derived β-cell lines.
506	23056550	We discovered that activation of the CCL2 gene by IL-1β required the p65 subunit of NF-κB and was dependent on genomic response elements located in the -3.6 kb region of the proximal gene promoter.
507	23056550	CCL2 gene transcription in response to IL-1β was blocked by pharmacological inhibition of the IKKβ and p38 MAPK pathways.
508	23056550	The IL-1β-mediated increase in CCL2 secretion was also impaired by p38 MAPK inhibition and by glucocorticoids.
509	23056550	Moreover, multiple synthetic glucocorticoids inhibited the IL-1β-stimulated induction of the CCL2 gene.
510	23056550	Induction of the MAP Kinase Phosphatase-1 (MKP-1) gene by glucocorticoids or by adenoviral-mediated overexpression decreased p38 MAPK phosphorylation, which diminished CCL2 gene expression, promoter activity, and release of CCL2 protein.
511	23056550	We conclude that glucocorticoid-mediated repression of IL-1β-induced CCL2 gene transcription and protein secretion occurs in part through the upregulation of the MKP-1 gene and subsequent deactivation of the p38 MAPK.
512	23056550	Furthermore, the anti-inflammatory actions observed with MKP-1 overexpression were obtained without suppressing glucose-stimulated insulin secretion.
513	23056550	Regulation of the CCL2 gene in pancreatic β-cells by IL-1β and glucocorticoids: role of MKP-1.
514	23056550	Therefore, we investigated the positive and negative regulatory components controlling expression of the CCL2 gene using isolated rat islets and INS-1-derived β-cell lines.
515	23056550	We discovered that activation of the CCL2 gene by IL-1β required the p65 subunit of NF-κB and was dependent on genomic response elements located in the -3.6 kb region of the proximal gene promoter.
516	23056550	CCL2 gene transcription in response to IL-1β was blocked by pharmacological inhibition of the IKKβ and p38 MAPK pathways.
517	23056550	The IL-1β-mediated increase in CCL2 secretion was also impaired by p38 MAPK inhibition and by glucocorticoids.
518	23056550	Moreover, multiple synthetic glucocorticoids inhibited the IL-1β-stimulated induction of the CCL2 gene.
519	23056550	Induction of the MAP Kinase Phosphatase-1 (MKP-1) gene by glucocorticoids or by adenoviral-mediated overexpression decreased p38 MAPK phosphorylation, which diminished CCL2 gene expression, promoter activity, and release of CCL2 protein.
520	23056550	We conclude that glucocorticoid-mediated repression of IL-1β-induced CCL2 gene transcription and protein secretion occurs in part through the upregulation of the MKP-1 gene and subsequent deactivation of the p38 MAPK.
521	23056550	Furthermore, the anti-inflammatory actions observed with MKP-1 overexpression were obtained without suppressing glucose-stimulated insulin secretion.
522	23144758	NADPH oxidase 4 mediates insulin-stimulated HIF-1α and VEGF expression, and angiogenesis in vitro.
523	23144758	Acute intensive insulin therapy causes a transient worsening of diabetic retinopathy in type 1 diabetes patients and is related to VEGF expression.
524	23144758	Reactive oxygen species (ROS) have been shown to be involved in HIF-1α and VEGF expression induced by insulin, but the role of specific ROS sources has not been fully elucidated.
525	23144758	In this study we examined the role of NADPH oxidase subunit 4 (Nox4) in insulin-stimulated HIF-1α and VEGF expression, and angiogenic responses in human microvascular endothelial cells (HMVECs).
526	23144758	Here we demonstrate that knockdown of Nox4 by siRNA reduced insulin-stimulated ROS generation, the tyrosine phosphorylation of IR-β and IRS-1, but did not change the serine phosphorylation of IRS-1.
527	23144758	Nox4 gene silencing had a much greater inhibitory effect on insulin-induced AKT activation than ERK1/2 activation, whereas it had little effect on the expression of the phosphatases such as MKP-1 and SHIP.
528	23144758	Inhibition of Nox4 expression inhibited the transcriptional activity of VEGF through HIF-1.
529	23144758	Overexpression of wild-type Nox4 was sufficient to increase VEGF transcriptional activity, and further enhanced insulin-stimulated the activation of VEGF.
530	23144758	Downregulation of Nox4 expression decreased insulin-stimulated mRNA and protein expression of HIF-1α, but did not change the rate of HIF-1α degradation.
531	23144758	Inhibition of Nox4 impaired insulin-stimulated VEGF expression, cell migration, cell proliferation, and tube formation in HMVECs.
532	23144758	Our data indicate that Nox4-derived ROS are essential for HIF-1α-dependent VEGF expression, and angiogenesis in vitro induced by insulin.
533	23144758	Nox4 may be an attractive therapeutic target for diabetic retinopathy caused by intensive insulin treatment.
534	23624822	Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity.
535	23624822	Moreover, CLCE treatment inhibited Dex-induced protein kinase B (PKB) dephosphorylation without affecting Dex-induced extracellular signal-regulated protein kinase-1/2 dephosphorylation and MKP-1 upregulation.
536	23624822	Importantly, the protective effect of CLCE on Dex-induced cytotoxicity in INS-1 cells was attenuated by LY294002, an inhibitor of PI3K/PKB.
537	23624822	Collectively, these findings demonstrate for the first time the ability of CLCE to specifically protect INS-1 cells from Dex-induced cytotoxicity through the modulation of the PI3K/PKB pathway.