Ignet

Gene Information

Gene symbol: PTPN6

Gene name: protein tyrosine phosphatase, non-receptor type 6

HGNC ID: 9658

Synonyms: HCP, HCPH, PTP-1C, SHP-1, SHP1

Related Genes

#	Gene Symbol	Number of hits
1	AKT1	1 hits
2	ANGPT1	1 hits
3	CASP3	1 hits
4	CBL	1 hits
5	CDC25A	1 hits
6	CDC25B	1 hits
7	CYP7A1	1 hits
8	DUSP3	1 hits
9	DUSP6	1 hits
10	HNF1A	1 hits
11	HNF4A	1 hits
12	HPN	1 hits
13	INS	1 hits
14	INSR	1 hits
15	IRF6	1 hits
16	JAK2	1 hits
17	JUN	1 hits
18	KDR	1 hits
19	MAPK1	1 hits
20	MAPK14	1 hits
21	NFKB1	1 hits
22	NOX5	1 hits
23	NR0B2	1 hits
24	NR1H4	1 hits
25	PARK2	1 hits
26	PDGFA	1 hits
27	PIK3CA	1 hits
28	PPP1R3C	1 hits
29	PRKCA	1 hits
30	PRKCD	1 hits
31	PTPN1	1 hits
32	PTPN11	1 hits
33	PTPN13	1 hits
34	PTPN2	1 hits
35	PTPN7	1 hits
36	PTPRA	1 hits
37	PTPRC	1 hits
38	PTPRF	1 hits
39	PTPRU	1 hits
40	RELA	1 hits
41	RELB	1 hits
42	SIRPA	1 hits
43	SRC	1 hits
44	SULT1A1	1 hits
45	TCF7	1 hits
46	TEK	1 hits
47	VEGFA	1 hits

Related Sentences

#	PMID	Sentence
1	11279518	Tcf1-/- liver has decreased expression of the basolateral membrane bile acid transporters Slc10a1, Slc21a3 and Slc21a5, leading to impaired portal bile acid uptake and elevated plasma bile acid concentrations.
2	11279518	In intestine and kidneys, Tcf1-/- mice lack expression of the ileal bile acid transporter (Slc10a2), resulting in increased fecal and urinary bile acid excretion.
3	11279518	The Tcf1 protein (also known as HNF-1alpha) also regulates transcription of the gene (Nr1h4) encoding the farnesoid X receptor-1 (Fxr-1), thereby leading to reduced expression of small heterodimer partner-1 (Shp-1) and repression of Cyp7a1, the rate-limiting enzyme in the classic bile acid biosynthesis pathway.
4	11279518	This is most likely due to reduced activity of the HDL-catabolic enzyme hepatic lipase (Lipc) and increased expression of HDL-cholesterol esterifying enzyme lecithin:cholesterol acyl transferase (Lcat).
5	11279518	Our studies demonstrate that Tcf1, in addition to being an important regulator of insulin secretion, is an essential transcriptional regulator of bile acid and HDL-cholesterol metabolism.
6	11584002	The combinatorial library/high-throughput screen protocols furnished a small molecule PTP1B inhibitor that is both potent (K(i) = 2.4 nm) and selective (little or no activity against a panel of phosphatases including Yersinia PTPase, SHP1, SHP2, LAR, HePTP, PTPalpha, CD45, VHR, MKP3, Cdc25A, Stp1, and PP2C).
7	11679424	We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice.
8	11679424	In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice.
9	11679424	This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice.
10	11679424	The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets.
11	11679424	We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha.
12	11679424	We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop.
13	11679424	We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice.
14	11679424	In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice.
15	11679424	This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice.
16	11679424	The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets.
17	11679424	We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha.
18	11679424	We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop.
19	11679424	We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice.
20	11679424	In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice.
21	11679424	This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice.
22	11679424	The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets.
23	11679424	We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha.
24	11679424	We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop.
25	12167615	SHPS-1 is a receptor-type glycoprotein that binds and activates the protein-tyrosine phosphatases SHP-1 and SHP-2, and thereby negatively modulates intracellular signaling initiated by various cell surface receptors coupled to tyrosine kinases.
26	12167615	SHPS-1 also regulates intercellular communication in the neural and immune systems through its association with CD47 (integrin-associated protein) on adjacent cells.
27	12186556	In this work, we have shown that certain aryl-substituted aldehydes act as reversible, slow-binding inhibitors of modest potency against PTP1B, SHP-1, and a dual-specificity phosphatase, VHR.
28	12186556	Similar experiments with Cinn-GEE that had been labeled with (13)C at the benzylic position revealed a change in the hybridization state (from sp(2) to sp(3)) for the benzylic carbon as a result of binding to PTP1B.
29	15554709	In this work, trans-beta-nitrostyrene (TBNS) and its derivatives are found to be slow-binding inhibitors against protein tyrosine phosphatases PTP1B, SHP-1, and Yop with moderate potencies (K(I*) = 1-10 microM).
30	15554709	These studies suggested a mechanism in which TBNS acts a pY mimetic and binds to the PTP active site to form an initial noncovalent E.I complex, followed by nucleophilic attack on the TBNS nitro group by Cys-215 of PTP1B to form a reversible, covalent adduct as the tighter E.I* complex.
31	17082646	DRlyp/lyp PLN mast cell gene expression profiling revealed an activated population and included significant overrepresentation of transcripts for mast cell protease 1, cationic trypsinogen, carboxypeptidase A, IL-5, and phospholipase Cgamma.
32	17082646	In the DR(+/+) rat, which develops T1DM upon depletion of T regulator cells, mast cells displayed gene expression consistent with the negative regulation of degranulation, including significant overrepresentation of transcripts encoding tyrosine phosphatase SHP-1, lipid phosphatase SHIP, and E3 ubiquitin ligase c-Cbl.
33	17647198	The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.
34	17647198	In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal protein-tyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions.
35	17647198	SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light.
36	17647198	SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer.
37	17647198	Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs.
38	17647198	SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB.
39	17647198	Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities.
40	17647198	The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.
41	17647198	In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal protein-tyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions.
42	17647198	SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light.
43	17647198	SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer.
44	17647198	Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs.
45	17647198	SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB.
46	17647198	Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities.
47	17647198	The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.
48	17647198	In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal protein-tyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions.
49	17647198	SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light.
50	17647198	SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer.
51	17647198	Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs.
52	17647198	SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB.
53	17647198	Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities.
54	17647198	The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.
55	17647198	In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal protein-tyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions.
56	17647198	SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light.
57	17647198	SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer.
58	17647198	Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs.
59	17647198	SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB.
60	17647198	Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities.
61	17647198	The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.
62	17647198	In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal protein-tyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions.
63	17647198	SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light.
64	17647198	SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer.
65	17647198	Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs.
66	17647198	SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB.
67	17647198	Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities.
68	17647198	The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.
69	17647198	In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal protein-tyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions.
70	17647198	SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light.
71	17647198	SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer.
72	17647198	Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs.
73	17647198	SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB.
74	17647198	Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities.
75	17647198	The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.
76	17647198	In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal protein-tyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions.
77	17647198	SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light.
78	17647198	SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer.
79	17647198	Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs.
80	17647198	SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB.
81	17647198	Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities.
82	18292540	In T1DM patients, late LPS-mediated nuclear DNA binding by RelA, p50, c-Rel, and RelB was impaired as compared with type 2 DM, rheumatoid arthritis, and healthy subjects, associated with impaired DC CD40 and MHC class I induction but normal cytokine production.
83	18292540	In TIDM monocytes, RelA and RelB were constitutively activated, and the src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), a negative regulator of NF-kappaB, was overexpressed.
84	18292540	Addition of sodium stibogluconate, a SHP-1 inhibitor, to DCs differentiating from monocyte precursors restored their capacity to respond to LPS in approximately 60% of patients.
85	18292540	The monocyte and DC NF-kappaB response to LPS is thus a novel phenotypic and likely pathogenetic marker for human T1DM.
86	18292540	SHP-1 is at least one NF-kappaB regulatory mechanism which might be induced as a result of abnormal inflammatory signaling responses in T1DM monocytes.
87	18292540	In T1DM patients, late LPS-mediated nuclear DNA binding by RelA, p50, c-Rel, and RelB was impaired as compared with type 2 DM, rheumatoid arthritis, and healthy subjects, associated with impaired DC CD40 and MHC class I induction but normal cytokine production.
88	18292540	In TIDM monocytes, RelA and RelB were constitutively activated, and the src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), a negative regulator of NF-kappaB, was overexpressed.
89	18292540	Addition of sodium stibogluconate, a SHP-1 inhibitor, to DCs differentiating from monocyte precursors restored their capacity to respond to LPS in approximately 60% of patients.
90	18292540	The monocyte and DC NF-kappaB response to LPS is thus a novel phenotypic and likely pathogenetic marker for human T1DM.
91	18292540	SHP-1 is at least one NF-kappaB regulatory mechanism which might be induced as a result of abnormal inflammatory signaling responses in T1DM monocytes.
92	18292540	In T1DM patients, late LPS-mediated nuclear DNA binding by RelA, p50, c-Rel, and RelB was impaired as compared with type 2 DM, rheumatoid arthritis, and healthy subjects, associated with impaired DC CD40 and MHC class I induction but normal cytokine production.
93	18292540	In TIDM monocytes, RelA and RelB were constitutively activated, and the src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), a negative regulator of NF-kappaB, was overexpressed.
94	18292540	Addition of sodium stibogluconate, a SHP-1 inhibitor, to DCs differentiating from monocyte precursors restored their capacity to respond to LPS in approximately 60% of patients.
95	18292540	The monocyte and DC NF-kappaB response to LPS is thus a novel phenotypic and likely pathogenetic marker for human T1DM.
96	18292540	SHP-1 is at least one NF-kappaB regulatory mechanism which might be induced as a result of abnormal inflammatory signaling responses in T1DM monocytes.
97	19881493	In the retina, pericyte apoptosis and the formation of acellular capillaries, the most specific vascular pathologies attributed to hyperglycemia, is linked to the loss of platelet-derived growth factor (PDGF)-mediated survival actions owing to unknown mechanisms.
98	19881493	Here we show that hyperglycemia persistently activates protein kinase C-delta (PKC-delta, encoded by Prkcd) and p38alpha mitogen-activated protein kinase (MAPK) to increase the expression of a previously unknown target of PKC-delta signaling, Src homology-2 domain-containing phosphatase-1 (SHP-1), a protein tyrosine phosphatase.
99	19881493	This signaling cascade leads to PDGF receptor-beta dephosphorylation and a reduction in downstream signaling from this receptor, resulting in pericyte apoptosis independently of nuclear factor-kappaB (NF-kappaB) signaling.
100	19881493	Unlike diabetic age-matched wild-type mice, diabetic Prkcd(-/-) mice did not show activation of p38alpha MAPK or SHP-1, inhibition of PDGF signaling in vascular cells or the presence of acellular capillaries.
101	19881493	We also observed PKC-delta, p38alpha MAPK and SHP-1 activation in brain pericytes and in the renal cortex of diabetic mice.
102	19881493	In the retina, pericyte apoptosis and the formation of acellular capillaries, the most specific vascular pathologies attributed to hyperglycemia, is linked to the loss of platelet-derived growth factor (PDGF)-mediated survival actions owing to unknown mechanisms.
103	19881493	Here we show that hyperglycemia persistently activates protein kinase C-delta (PKC-delta, encoded by Prkcd) and p38alpha mitogen-activated protein kinase (MAPK) to increase the expression of a previously unknown target of PKC-delta signaling, Src homology-2 domain-containing phosphatase-1 (SHP-1), a protein tyrosine phosphatase.
104	19881493	This signaling cascade leads to PDGF receptor-beta dephosphorylation and a reduction in downstream signaling from this receptor, resulting in pericyte apoptosis independently of nuclear factor-kappaB (NF-kappaB) signaling.
105	19881493	Unlike diabetic age-matched wild-type mice, diabetic Prkcd(-/-) mice did not show activation of p38alpha MAPK or SHP-1, inhibition of PDGF signaling in vascular cells or the presence of acellular capillaries.
106	19881493	We also observed PKC-delta, p38alpha MAPK and SHP-1 activation in brain pericytes and in the renal cortex of diabetic mice.
107	19881493	In the retina, pericyte apoptosis and the formation of acellular capillaries, the most specific vascular pathologies attributed to hyperglycemia, is linked to the loss of platelet-derived growth factor (PDGF)-mediated survival actions owing to unknown mechanisms.
108	19881493	Here we show that hyperglycemia persistently activates protein kinase C-delta (PKC-delta, encoded by Prkcd) and p38alpha mitogen-activated protein kinase (MAPK) to increase the expression of a previously unknown target of PKC-delta signaling, Src homology-2 domain-containing phosphatase-1 (SHP-1), a protein tyrosine phosphatase.
109	19881493	This signaling cascade leads to PDGF receptor-beta dephosphorylation and a reduction in downstream signaling from this receptor, resulting in pericyte apoptosis independently of nuclear factor-kappaB (NF-kappaB) signaling.
110	19881493	Unlike diabetic age-matched wild-type mice, diabetic Prkcd(-/-) mice did not show activation of p38alpha MAPK or SHP-1, inhibition of PDGF signaling in vascular cells or the presence of acellular capillaries.
111	19881493	We also observed PKC-delta, p38alpha MAPK and SHP-1 activation in brain pericytes and in the renal cortex of diabetic mice.
112	20064934	Using a gain-of-function model of endothelial nitric-oxide synthase (eNOS)-transfected COS-7 cells, we have shown a critical role of NO in insulin responsiveness, as evidenced by an NO-dependent increase of tyrosine phosphorylation levels of the insulin receptor and its downstream effectors insulin receptor substrate-1 and PKB/AKT.
113	20064934	We hypothesized that NO-induced inactivation of endogenous protein-tyrosine phosphatases (PTPs) would enhance insulin receptor-mediated signaling.
114	20064934	Our data suggest that phosphatases SHP-1, SHP-2, and PTP1B, but not TC-PTP, are likely S-nitrosylated at the active site cysteine residue concomitantly with a burst of NO production in signaling response to insulin stimulation.
115	20064934	We investigated further the role of NO as a regulator of insulin signaling by RNA interference that ablates endogenous eNOS expression in endothelial MS-1 cells.
116	20064934	We have shown that eNOS-dependent NO production is essential for the activation of insulin signaling.
117	20864515	Prep1 controls insulin glucoregulatory function in liver by transcriptional targeting of SHP1 tyrosine phosphatase.
118	21251827	Successive biological assay identified these glycopeptidotriazoles as favorable PTP1B and CDC25B inhibitors with selectivity over TCPTP, LAR, SHP-1 and SHP-2.
119	21251827	Docking simulation was eventually conducted to propose plausible binding modes of this compound series with PTP1B and CDC25B.
120	22454630	Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.
121	22454630	Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis.
122	22454630	Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation.
123	22454630	In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis.
124	22454630	Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC).
125	22454630	Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation.
126	22454630	Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation.
127	22454630	Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC.
128	22454630	Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis.
129	22454630	Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.
130	22454630	Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.
131	22454630	Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis.
132	22454630	Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation.
133	22454630	In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis.
134	22454630	Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC).
135	22454630	Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation.
136	22454630	Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation.
137	22454630	Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC.
138	22454630	Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis.
139	22454630	Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.
140	22454630	Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.
141	22454630	Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis.
142	22454630	Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation.
143	22454630	In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis.
144	22454630	Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC).
145	22454630	Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation.
146	22454630	Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation.
147	22454630	Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC.
148	22454630	Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis.
149	22454630	Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.
150	22454630	Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.
151	22454630	Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis.
152	22454630	Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation.
153	22454630	In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis.
154	22454630	Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC).
155	22454630	Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation.
156	22454630	Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation.
157	22454630	Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC.
158	22454630	Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis.
159	22454630	Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.
160	22454630	Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.
161	22454630	Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis.
162	22454630	Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation.
163	22454630	In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis.
164	22454630	Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC).
165	22454630	Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation.
166	22454630	Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation.
167	22454630	Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC.
168	22454630	Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis.
169	22454630	Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.
170	22454630	Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.
171	22454630	Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis.
172	22454630	Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation.
173	22454630	In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis.
174	22454630	Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC).
175	22454630	Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation.
176	22454630	Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation.
177	22454630	Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC.
178	22454630	Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis.
179	22454630	Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.
180	22499584	Glomerular VEGF resistance induced by PKCδ/SHP-1 activation and contribution to diabetic nephropathy.
181	22499584	This study characterizes the effect of glucose-induced activation of protein kinase Cδ (PKCδ) and Src homology-2 domain-containing phosphatase-1 (SHP-1) expression on vascular endothelial growth factor (VEGF) actions in glomerular podocytes in cultures and in glomeruli of diabetic rodents.
182	22499584	Elevation of glucose levels induced PKCδ and p38 mitogen-activated protein kinase (p38 MAPK) to increase SHP-1 expression, increased podocyte apoptosis, and inhibited VEGF activation in podocytes and glomerular endothelial cells.
183	22499584	Increased PKCδ activation and SHP-1 expression correlated with loss of VEGF signaling and podocyte numbers in the glomeruli of diabetic rats and mice.
184	22499584	In contrast, diabetic PKCδ-knockout (Prkcd(-/-)) mice did not exhibit activation of p38 MAPK and SHP-1 or inhibition of VEGF signaling in renal glomeruli.
185	22499584	Functionally, diabetic Prkcd(-/-) mice had decreased expressions of TGFβ, VEGF, and extracellular matrix and less albuminuria than diabetic Prkcd(+/+) mice.
186	22499584	Hyperglycemia and diabetes can cause glomerular podocyte apoptosis and endothelial dysfunction partly due to increased PKCδ/p38 MAPK activation and the expression of SHP-1 to cause VEGF resistance, independent of NF-κB activation.
187	22499584	Glomerular VEGF resistance induced by PKCδ/SHP-1 activation and contribution to diabetic nephropathy.
188	22499584	This study characterizes the effect of glucose-induced activation of protein kinase Cδ (PKCδ) and Src homology-2 domain-containing phosphatase-1 (SHP-1) expression on vascular endothelial growth factor (VEGF) actions in glomerular podocytes in cultures and in glomeruli of diabetic rodents.
189	22499584	Elevation of glucose levels induced PKCδ and p38 mitogen-activated protein kinase (p38 MAPK) to increase SHP-1 expression, increased podocyte apoptosis, and inhibited VEGF activation in podocytes and glomerular endothelial cells.
190	22499584	Increased PKCδ activation and SHP-1 expression correlated with loss of VEGF signaling and podocyte numbers in the glomeruli of diabetic rats and mice.
191	22499584	In contrast, diabetic PKCδ-knockout (Prkcd(-/-)) mice did not exhibit activation of p38 MAPK and SHP-1 or inhibition of VEGF signaling in renal glomeruli.
192	22499584	Functionally, diabetic Prkcd(-/-) mice had decreased expressions of TGFβ, VEGF, and extracellular matrix and less albuminuria than diabetic Prkcd(+/+) mice.
193	22499584	Hyperglycemia and diabetes can cause glomerular podocyte apoptosis and endothelial dysfunction partly due to increased PKCδ/p38 MAPK activation and the expression of SHP-1 to cause VEGF resistance, independent of NF-κB activation.
194	22499584	Glomerular VEGF resistance induced by PKCδ/SHP-1 activation and contribution to diabetic nephropathy.
195	22499584	This study characterizes the effect of glucose-induced activation of protein kinase Cδ (PKCδ) and Src homology-2 domain-containing phosphatase-1 (SHP-1) expression on vascular endothelial growth factor (VEGF) actions in glomerular podocytes in cultures and in glomeruli of diabetic rodents.
196	22499584	Elevation of glucose levels induced PKCδ and p38 mitogen-activated protein kinase (p38 MAPK) to increase SHP-1 expression, increased podocyte apoptosis, and inhibited VEGF activation in podocytes and glomerular endothelial cells.
197	22499584	Increased PKCδ activation and SHP-1 expression correlated with loss of VEGF signaling and podocyte numbers in the glomeruli of diabetic rats and mice.
198	22499584	In contrast, diabetic PKCδ-knockout (Prkcd(-/-)) mice did not exhibit activation of p38 MAPK and SHP-1 or inhibition of VEGF signaling in renal glomeruli.
199	22499584	Functionally, diabetic Prkcd(-/-) mice had decreased expressions of TGFβ, VEGF, and extracellular matrix and less albuminuria than diabetic Prkcd(+/+) mice.
200	22499584	Hyperglycemia and diabetes can cause glomerular podocyte apoptosis and endothelial dysfunction partly due to increased PKCδ/p38 MAPK activation and the expression of SHP-1 to cause VEGF resistance, independent of NF-κB activation.
201	22499584	Glomerular VEGF resistance induced by PKCδ/SHP-1 activation and contribution to diabetic nephropathy.
202	22499584	This study characterizes the effect of glucose-induced activation of protein kinase Cδ (PKCδ) and Src homology-2 domain-containing phosphatase-1 (SHP-1) expression on vascular endothelial growth factor (VEGF) actions in glomerular podocytes in cultures and in glomeruli of diabetic rodents.
203	22499584	Elevation of glucose levels induced PKCδ and p38 mitogen-activated protein kinase (p38 MAPK) to increase SHP-1 expression, increased podocyte apoptosis, and inhibited VEGF activation in podocytes and glomerular endothelial cells.
204	22499584	Increased PKCδ activation and SHP-1 expression correlated with loss of VEGF signaling and podocyte numbers in the glomeruli of diabetic rats and mice.
205	22499584	In contrast, diabetic PKCδ-knockout (Prkcd(-/-)) mice did not exhibit activation of p38 MAPK and SHP-1 or inhibition of VEGF signaling in renal glomeruli.
206	22499584	Functionally, diabetic Prkcd(-/-) mice had decreased expressions of TGFβ, VEGF, and extracellular matrix and less albuminuria than diabetic Prkcd(+/+) mice.
207	22499584	Hyperglycemia and diabetes can cause glomerular podocyte apoptosis and endothelial dysfunction partly due to increased PKCδ/p38 MAPK activation and the expression of SHP-1 to cause VEGF resistance, independent of NF-κB activation.
208	22499584	Glomerular VEGF resistance induced by PKCδ/SHP-1 activation and contribution to diabetic nephropathy.
209	22499584	This study characterizes the effect of glucose-induced activation of protein kinase Cδ (PKCδ) and Src homology-2 domain-containing phosphatase-1 (SHP-1) expression on vascular endothelial growth factor (VEGF) actions in glomerular podocytes in cultures and in glomeruli of diabetic rodents.
210	22499584	Elevation of glucose levels induced PKCδ and p38 mitogen-activated protein kinase (p38 MAPK) to increase SHP-1 expression, increased podocyte apoptosis, and inhibited VEGF activation in podocytes and glomerular endothelial cells.
211	22499584	Increased PKCδ activation and SHP-1 expression correlated with loss of VEGF signaling and podocyte numbers in the glomeruli of diabetic rats and mice.
212	22499584	In contrast, diabetic PKCδ-knockout (Prkcd(-/-)) mice did not exhibit activation of p38 MAPK and SHP-1 or inhibition of VEGF signaling in renal glomeruli.
213	22499584	Functionally, diabetic Prkcd(-/-) mice had decreased expressions of TGFβ, VEGF, and extracellular matrix and less albuminuria than diabetic Prkcd(+/+) mice.
214	22499584	Hyperglycemia and diabetes can cause glomerular podocyte apoptosis and endothelial dysfunction partly due to increased PKCδ/p38 MAPK activation and the expression of SHP-1 to cause VEGF resistance, independent of NF-κB activation.
215	22499584	Glomerular VEGF resistance induced by PKCδ/SHP-1 activation and contribution to diabetic nephropathy.
216	22499584	This study characterizes the effect of glucose-induced activation of protein kinase Cδ (PKCδ) and Src homology-2 domain-containing phosphatase-1 (SHP-1) expression on vascular endothelial growth factor (VEGF) actions in glomerular podocytes in cultures and in glomeruli of diabetic rodents.
217	22499584	Elevation of glucose levels induced PKCδ and p38 mitogen-activated protein kinase (p38 MAPK) to increase SHP-1 expression, increased podocyte apoptosis, and inhibited VEGF activation in podocytes and glomerular endothelial cells.
218	22499584	Increased PKCδ activation and SHP-1 expression correlated with loss of VEGF signaling and podocyte numbers in the glomeruli of diabetic rats and mice.
219	22499584	In contrast, diabetic PKCδ-knockout (Prkcd(-/-)) mice did not exhibit activation of p38 MAPK and SHP-1 or inhibition of VEGF signaling in renal glomeruli.
220	22499584	Functionally, diabetic Prkcd(-/-) mice had decreased expressions of TGFβ, VEGF, and extracellular matrix and less albuminuria than diabetic Prkcd(+/+) mice.
221	22499584	Hyperglycemia and diabetes can cause glomerular podocyte apoptosis and endothelial dysfunction partly due to increased PKCδ/p38 MAPK activation and the expression of SHP-1 to cause VEGF resistance, independent of NF-κB activation.
222	22553146	Advanced glycation end product Nε-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1-regulated VEGFR-2 dephosphorylation.
223	22553146	Here, we tested the hypothesis that NADPH oxidase/reactive oxygen species (ROS)-mediated SH2 domain-containing tyrosine phosphatase-1 (SHP-1) activation by CML inhibits the VEGF receptor-2 (VEGFR-2, KDR/Flk-1) activation, resulting in HUVEC injury.
224	22553146	CML significantly inhibited cell proliferation and induced apoptosis and reduced VEGFR-2 activation in parallel with the increased SHP-1 protein expression and activity in HUVECs.
225	22553146	Exposure of HUVECs to CML also remarkably escalated the integration of SHP-1 with VEGFR-2.
226	22553146	We conclude that a pathway of tyrosine phosphatase SHP-1-regulated VEGFR-2 dephosphorylation through NADPH oxidase-derived ROS is involved in the CML-triggered endothelial cell dysfunction/injury.
227	22553146	Advanced glycation end product Nε-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1-regulated VEGFR-2 dephosphorylation.
228	22553146	Here, we tested the hypothesis that NADPH oxidase/reactive oxygen species (ROS)-mediated SH2 domain-containing tyrosine phosphatase-1 (SHP-1) activation by CML inhibits the VEGF receptor-2 (VEGFR-2, KDR/Flk-1) activation, resulting in HUVEC injury.
229	22553146	CML significantly inhibited cell proliferation and induced apoptosis and reduced VEGFR-2 activation in parallel with the increased SHP-1 protein expression and activity in HUVECs.
230	22553146	Exposure of HUVECs to CML also remarkably escalated the integration of SHP-1 with VEGFR-2.
231	22553146	We conclude that a pathway of tyrosine phosphatase SHP-1-regulated VEGFR-2 dephosphorylation through NADPH oxidase-derived ROS is involved in the CML-triggered endothelial cell dysfunction/injury.
232	22553146	Advanced glycation end product Nε-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1-regulated VEGFR-2 dephosphorylation.
233	22553146	Here, we tested the hypothesis that NADPH oxidase/reactive oxygen species (ROS)-mediated SH2 domain-containing tyrosine phosphatase-1 (SHP-1) activation by CML inhibits the VEGF receptor-2 (VEGFR-2, KDR/Flk-1) activation, resulting in HUVEC injury.
234	22553146	CML significantly inhibited cell proliferation and induced apoptosis and reduced VEGFR-2 activation in parallel with the increased SHP-1 protein expression and activity in HUVECs.
235	22553146	Exposure of HUVECs to CML also remarkably escalated the integration of SHP-1 with VEGFR-2.
236	22553146	We conclude that a pathway of tyrosine phosphatase SHP-1-regulated VEGFR-2 dephosphorylation through NADPH oxidase-derived ROS is involved in the CML-triggered endothelial cell dysfunction/injury.
237	22553146	Advanced glycation end product Nε-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1-regulated VEGFR-2 dephosphorylation.
238	22553146	Here, we tested the hypothesis that NADPH oxidase/reactive oxygen species (ROS)-mediated SH2 domain-containing tyrosine phosphatase-1 (SHP-1) activation by CML inhibits the VEGF receptor-2 (VEGFR-2, KDR/Flk-1) activation, resulting in HUVEC injury.
239	22553146	CML significantly inhibited cell proliferation and induced apoptosis and reduced VEGFR-2 activation in parallel with the increased SHP-1 protein expression and activity in HUVECs.
240	22553146	Exposure of HUVECs to CML also remarkably escalated the integration of SHP-1 with VEGFR-2.
241	22553146	We conclude that a pathway of tyrosine phosphatase SHP-1-regulated VEGFR-2 dephosphorylation through NADPH oxidase-derived ROS is involved in the CML-triggered endothelial cell dysfunction/injury.
242	22553146	Advanced glycation end product Nε-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1-regulated VEGFR-2 dephosphorylation.
243	22553146	Here, we tested the hypothesis that NADPH oxidase/reactive oxygen species (ROS)-mediated SH2 domain-containing tyrosine phosphatase-1 (SHP-1) activation by CML inhibits the VEGF receptor-2 (VEGFR-2, KDR/Flk-1) activation, resulting in HUVEC injury.
244	22553146	CML significantly inhibited cell proliferation and induced apoptosis and reduced VEGFR-2 activation in parallel with the increased SHP-1 protein expression and activity in HUVECs.
245	22553146	Exposure of HUVECs to CML also remarkably escalated the integration of SHP-1 with VEGFR-2.
246	22553146	We conclude that a pathway of tyrosine phosphatase SHP-1-regulated VEGFR-2 dephosphorylation through NADPH oxidase-derived ROS is involved in the CML-triggered endothelial cell dysfunction/injury.
247	22698917	Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
248	22698917	The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined.
249	22698917	To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding.
250	22698917	When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity.
251	22698917	After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations.
252	22698917	Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion.
253	22698917	Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver.
254	22698917	These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
255	22698917	Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
256	22698917	The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined.
257	22698917	To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding.
258	22698917	When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity.
259	22698917	After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations.
260	22698917	Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion.
261	22698917	Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver.
262	22698917	These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
263	22698917	Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
264	22698917	The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined.
265	22698917	To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding.
266	22698917	When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity.
267	22698917	After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations.
268	22698917	Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion.
269	22698917	Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver.
270	22698917	These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
271	22698917	Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
272	22698917	The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined.
273	22698917	To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding.
274	22698917	When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity.
275	22698917	After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations.
276	22698917	Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion.
277	22698917	Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver.
278	22698917	These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
279	22698917	Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
280	22698917	The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined.
281	22698917	To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding.
282	22698917	When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity.
283	22698917	After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations.
284	22698917	Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion.
285	22698917	Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver.
286	22698917	These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
287	22698917	Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
288	22698917	The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined.
289	22698917	To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding.
290	22698917	When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity.
291	22698917	After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations.
292	22698917	Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion.
293	22698917	Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver.
294	22698917	These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
295	22698917	Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
296	22698917	The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined.
297	22698917	To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding.
298	22698917	When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity.
299	22698917	After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations.
300	22698917	Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion.
301	22698917	Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver.
302	22698917	These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
303	22698917	Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance.
304	22698917	The protein-tyrosine phosphatase Shp1 negatively regulates insulin action on glucose homeostasis in liver and muscle, but its potential role in obesity-linked insulin resistance has not been examined.
305	22698917	To investigate the role of Shp1 in hepatic insulin resistance, we generated hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)), which were subjected to extensive metabolic monitoring throughout an 8-week standard chow diet (SD) or high-fat diet (HFD) feeding.
306	22698917	When compared with their Shp1-expressing Ptpn6(f/f) littermates, Ptpn6(H-KO) mice exhibited significantly lowered fasting glycemia and heightened hepatic insulin sensitivity.
307	22698917	After HFD feeding, Ptpn6(H-KO) mice developed comparable levels of obesity as Ptpn6(f/f) mice, but they were remarkably protected from liver insulin resistance, as revealed by euglycemic clamps and hepatic insulin signaling determinations.
308	22698917	Although Ptpn6(H-KO) mice still acquired diet-induced peripheral insulin resistance, they were less hyperinsulinemic during a glucose tolerance test because of reduced insulin secretion.
309	22698917	Ptpn6(H-KO) mice also exhibited increased insulin clearance in line with enhanced CC1 tyrosine phosphorylation in liver.
310	22698917	These results show that hepatocyte Shp1 plays a critical role in the development of hepatic insulin resistance and represents a novel therapeutic target for obesity-linked diabetes.
311	23364683	The in vitro assay showed that HPN exhibited enhanced inhibitory activity against PTP1B with IC(50) 0.63 μmol/L and high selectivity against other PTPs (T cell protein tyrosine phosphatase (TCPTP), leucocyte antigen-related tyrosine phosphatase (LAR), Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) and SHP-2).
312	23364683	Western blotting results showed that HPN decreased PTP1B levels in pancreatic tissue.
313	23531619	Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes.
314	23531619	Previous studies demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes.
315	23531619	In contrast to Ins2(+/+) mice, insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were remarkably reduced in renal podocytes of Akita mice.
316	23531619	This renal insulin resistance was associated with elevated SHP-1 expression in the glomeruli.
317	23531619	HG exposure raised mRNA and protein levels of SHP-1 and reduced the insulin-signaling pathway in podocytes.
318	23531619	Overexpression of dominant-negative SHP-1 in podocytes prevented HG effects and restored insulin actions.
319	23531619	Elevated SHP-1 expression induced by high glucose levels was directly associated with insulin receptor-β in vitro and in vivo to prevent insulin-stimulated Akt and ERK phosphorylation.
320	23531619	In conclusion, our results showed that high levels of SHP-1 expression in glomeruli cause insulin resistance and podocyte loss, thereby contributing to diabetic nephropathy.
321	23531619	Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes.
322	23531619	Previous studies demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes.
323	23531619	In contrast to Ins2(+/+) mice, insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were remarkably reduced in renal podocytes of Akita mice.
324	23531619	This renal insulin resistance was associated with elevated SHP-1 expression in the glomeruli.
325	23531619	HG exposure raised mRNA and protein levels of SHP-1 and reduced the insulin-signaling pathway in podocytes.
326	23531619	Overexpression of dominant-negative SHP-1 in podocytes prevented HG effects and restored insulin actions.
327	23531619	Elevated SHP-1 expression induced by high glucose levels was directly associated with insulin receptor-β in vitro and in vivo to prevent insulin-stimulated Akt and ERK phosphorylation.
328	23531619	In conclusion, our results showed that high levels of SHP-1 expression in glomeruli cause insulin resistance and podocyte loss, thereby contributing to diabetic nephropathy.
329	23531619	Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes.
330	23531619	Previous studies demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes.
331	23531619	In contrast to Ins2(+/+) mice, insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were remarkably reduced in renal podocytes of Akita mice.
332	23531619	This renal insulin resistance was associated with elevated SHP-1 expression in the glomeruli.
333	23531619	HG exposure raised mRNA and protein levels of SHP-1 and reduced the insulin-signaling pathway in podocytes.
334	23531619	Overexpression of dominant-negative SHP-1 in podocytes prevented HG effects and restored insulin actions.
335	23531619	Elevated SHP-1 expression induced by high glucose levels was directly associated with insulin receptor-β in vitro and in vivo to prevent insulin-stimulated Akt and ERK phosphorylation.
336	23531619	In conclusion, our results showed that high levels of SHP-1 expression in glomeruli cause insulin resistance and podocyte loss, thereby contributing to diabetic nephropathy.
337	23531619	Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes.
338	23531619	Previous studies demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes.
339	23531619	In contrast to Ins2(+/+) mice, insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were remarkably reduced in renal podocytes of Akita mice.
340	23531619	This renal insulin resistance was associated with elevated SHP-1 expression in the glomeruli.
341	23531619	HG exposure raised mRNA and protein levels of SHP-1 and reduced the insulin-signaling pathway in podocytes.
342	23531619	Overexpression of dominant-negative SHP-1 in podocytes prevented HG effects and restored insulin actions.
343	23531619	Elevated SHP-1 expression induced by high glucose levels was directly associated with insulin receptor-β in vitro and in vivo to prevent insulin-stimulated Akt and ERK phosphorylation.
344	23531619	In conclusion, our results showed that high levels of SHP-1 expression in glomeruli cause insulin resistance and podocyte loss, thereby contributing to diabetic nephropathy.
345	23531619	Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes.
346	23531619	Previous studies demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes.
347	23531619	In contrast to Ins2(+/+) mice, insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were remarkably reduced in renal podocytes of Akita mice.
348	23531619	This renal insulin resistance was associated with elevated SHP-1 expression in the glomeruli.
349	23531619	HG exposure raised mRNA and protein levels of SHP-1 and reduced the insulin-signaling pathway in podocytes.
350	23531619	Overexpression of dominant-negative SHP-1 in podocytes prevented HG effects and restored insulin actions.
351	23531619	Elevated SHP-1 expression induced by high glucose levels was directly associated with insulin receptor-β in vitro and in vivo to prevent insulin-stimulated Akt and ERK phosphorylation.
352	23531619	In conclusion, our results showed that high levels of SHP-1 expression in glomeruli cause insulin resistance and podocyte loss, thereby contributing to diabetic nephropathy.
353	23531619	Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes.
354	23531619	Previous studies demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes.
355	23531619	In contrast to Ins2(+/+) mice, insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were remarkably reduced in renal podocytes of Akita mice.
356	23531619	This renal insulin resistance was associated with elevated SHP-1 expression in the glomeruli.
357	23531619	HG exposure raised mRNA and protein levels of SHP-1 and reduced the insulin-signaling pathway in podocytes.
358	23531619	Overexpression of dominant-negative SHP-1 in podocytes prevented HG effects and restored insulin actions.
359	23531619	Elevated SHP-1 expression induced by high glucose levels was directly associated with insulin receptor-β in vitro and in vivo to prevent insulin-stimulated Akt and ERK phosphorylation.
360	23531619	In conclusion, our results showed that high levels of SHP-1 expression in glomeruli cause insulin resistance and podocyte loss, thereby contributing to diabetic nephropathy.
361	23531619	Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes.
362	23531619	Previous studies demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes.
363	23531619	In contrast to Ins2(+/+) mice, insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation were remarkably reduced in renal podocytes of Akita mice.
364	23531619	This renal insulin resistance was associated with elevated SHP-1 expression in the glomeruli.
365	23531619	HG exposure raised mRNA and protein levels of SHP-1 and reduced the insulin-signaling pathway in podocytes.
366	23531619	Overexpression of dominant-negative SHP-1 in podocytes prevented HG effects and restored insulin actions.
367	23531619	Elevated SHP-1 expression induced by high glucose levels was directly associated with insulin receptor-β in vitro and in vivo to prevent insulin-stimulated Akt and ERK phosphorylation.
368	23531619	In conclusion, our results showed that high levels of SHP-1 expression in glomeruli cause insulin resistance and podocyte loss, thereby contributing to diabetic nephropathy.
369	23557702	Hyperglycemia is known to activate protein kinase C (PKC), affecting the expression and activity of growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).
370	23557702	VEGF and PDGF mRNA and protein expression were decreased in the muscles of diabetic Prkcd(+/+) mice and were normalized in diabetic Prkcd(-/-) mice.
371	23557702	Furthermore, phosphorylation of VEGF receptor 2 (VEGFR2) and PDGF receptor-β (PDGFR-β) were blunted in diabetic Prkcd(+/+) mice but elevated in diabetic Prkcd(-/-) mice.
372	23557702	The inhibition of VEGFR2 and PDGFR-β activity was associated with increased SHP-1 expression.