Ignet

Gene Information

Gene symbol: SHC1

Gene name: SHC (Src homology 2 domain containing) transforming protein 1

HGNC ID: 10840

Synonyms: p66

Related Genes

#	Gene Symbol	Number of hits
1	AGT	1 hits
2	CCK	1 hits
3	EDN1	1 hits
4	EGF	1 hits
5	EGFR	1 hits
6	EPHB2	1 hits
7	ERBB4	1 hits
8	FLNA	1 hits
9	FOXO3	1 hits
10	GRB2	1 hits
11	IGF1	1 hits
12	IL4	1 hits
13	INS	1 hits
14	INSR	1 hits
15	IRS1	1 hits
16	IRS2	1 hits
17	MAPK1	1 hits
18	MCM8	1 hits
19	NR0B2	1 hits
20	NTRK1	1 hits
21	PIK3R1	1 hits
22	PPP1R13B	1 hits
23	RORC	1 hits
24	RPS6KB1	1 hits
25	SIRPA	1 hits
26	SIRT1	1 hits
27	SOD2	1 hits
28	SRC	1 hits
29	TNF	1 hits
30	UBASH3B	1 hits

Related Sentences

#	PMID	Sentence
1	8196603	Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase.
2	7543098	Shc phosphorylation in cells following growth factor, insulin, cytokine, and lymphocyte receptor activation leads to its association with Grb2 and activation of Ras.
3	7499194	Phosphopeptide assays developed to compare PTB domain specificities show that the Shc PTB domain binds with highest affinity to psi XN beta 1 beta 2 pY motifs derived from middle T (mT), TrkA, ErbB4, or epidermal growth factor receptors (psi = hydrophobic, beta = beta-turn forming); the IRS-1 PTB domain does not bind with this motif.
4	7499194	In contrast, both the Shc and IRS-1 PTB domains bind psi psi psi XXN beta 1 beta 2pY sequences derived from insulin and interleukin 4 receptors, although specificities vary in detail.
5	8910437	This resulted in an increased association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, increased phosphatidylinositol 3-kinase activity in anti-IRS-1 immunoprecipitates, constitutive activation of p70 S6 protein kinase, and an increased association of Grb2 with Shc in the absence of ligand.
6	8910437	In addition, Grb2 association with Shc and activation of MAPK and the p70 S6 kinase were insensitive to insulin stimulation.
7	8910437	By contrast, association of Grb2 with Shc and activation of MAPK, but not the p70 S6 kinase, could be stimulated by epidermal growth factor or platelet-derived growth factor.
8	9468528	Insulin-like growth factor-I (IGF-I) receptors activate divergent signaling pathways by phosphorylating multiple cellular proteins, including insulin receptor substrate-1 (IRS-1) and the Shc proteins.
9	9468528	This study investigates the relationship between IGF-I receptor internalization and signaling via IRS-1 and Shc.
10	9468528	Low temperature (15 degrees C) decreased IGF-I receptor internalization and completely inhibited Shc phosphorylation.
11	10764814	Insulin binding to the insulin receptor (IR) triggers its autophosphorylation, resulting in phosphorylation of Shc and the downstream activation of p42/p44 extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2), which mediates insulin-induced proliferation in vascular smooth muscle cells (VSMC).
12	10764814	Insulin-induced phosphorylation of Shc was inhibited by TNFalpha in a similar pattern.
13	10764814	Thus, TNFalpha selectively interferes with insulin-induced mitogenic signaling by inhibiting the phosphorylation of Shc and the downstream activation of ERK1/2.
14	12138086	EGF increased the tyrosine phosphorylation of several proteins (the EGF receptor, insulin receptor substrate (IRS)-1, IRS-2, and Grb2-associated binder 1), whereas Shc and Gab2 were only weakly and inconsistently phosphorylated. p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase), was also found to associate with all of these docking molecules, showing that EGF activated PI 3-kinase pools that were additional to those of insulin.
15	12734206	We report here that human melanoma M2 cells lacking FLNa expression exhibited normal insulin receptor (IR) signaling, whereas FLNa-expressing A7 cells were unable to elicit insulin-dependent Shc tyrosine phosphorylation and p42/44 MAPK activation despite no significant defect in IR-stimulated phosphorylation of insulin receptor substrate-1 or activation of the phosphatidylinositol 3-kinase/AKT cascade.
16	12734206	Insulin-dependent translocation of Shc, SOS1, and MAPK to lipid raft microdomains was markedly attenuated by FLNa expression.
17	12970360	HGA did not affect either insulin receptor kinase activity or insulin-induced Shc phosphorylation on tyrosine.
18	15998704	The aim of the present study was 2-fold: (1) to characterize the cardiovascular phenotype of p66Shc knockout mice (p66Shc(-/-)), and (2) to test the novel hypothesis that disrupting the p66Shc might protect the heart from the damaging action of elevated Ang II levels.
19	15998704	In p66Shc(+/+), infusion of a sub-pressor dose of Ang II (300 nmol/kg body weight [BW] daily for 28 days) caused left ventricular hypertrophy and apoptotic death of cardiomyocytes and endothelial cells.
20	15998704	Consistently, in vitro experiments showed that Ang II causes apoptotic death of cardiomyocytes isolated from p66Shc(+/+) hearts to a greater extent as compared with p66Shc(-/-) cardiomyocytes.
21	15998704	In perspective, p66Shc inhibition may be envisioned as a novel way to prevent the deleterious effects of Ang II on the heart.
22	17652764	Phosphorylation of the adaptor protein Shc (Src homology 2 domain containing) transforming protein 1) was increased in RECs grown in high glucose.
23	17652764	For Shc to be phosphorylated, it must be recruited to the cytoplasmic domain of the transmembrane protein SHPS-1 (SHP substrate-1).
24	17652764	Shc recruitment to SHPS-1 was increased when RECs were grown in high glucose.
25	20689155	Recent findings that the pro-aging and pro-oxidant molecule p66shc contributes to S6K activation by nutrients and promotes insulin resistance and diabetes in mice may provide an answer to the "ROS or TOR?"
26	20624962	Biochemical studies revealed that p66shc promotes the signal-inhibitory phosphorylation of the major insulin transducer IRS-1, by bridging IRS-1 and the mTOR effector p70S6 kinase, a molecule previously linked to obesity-induced insulin resistance.
27	20624962	Importantly, IRS-1 was strongly up-regulated in the adipose tissue of p66KO lepOb/Ob mice, confirming that effects of p66 on tissue responsiveness to insulin are largely mediated by this molecule.
28	21778425	Objective: In this study, we investigated the role of SIRT1, a class III histone deacetylase, in the regulation of p66Shc expression and hyperglycemia-induced endothelial dysfunction.
29	21778425	Knockdown of SIRT1 increased p66Shc expression and also increased the expression levels of plasminogen activator inhibitor-1 expression, but decreased manganese superoxide dismutase expression in high-glucose conditions.
30	21778425	However, knockdown of p66Shc significantly reversed the effects of SIRT1 knockdown.
31	21778425	Our findings indicate that repression of p66Shc expression by SIRT1 contributes to the protection of hyperglycemia-induced endothelial dysfunction.
32	21893988	ET-1 is a potent mitogen of mesangial cells and the ability of ET-1 to support mesangial cell proliferation is likely to be associated with both recruitment of cytoplasmic tyrosine kinases which activate the Shc-Sos-Ras-Raf-MEK-ERK signaling pathway and transactivation of the EGF receptor.
33	21893988	The guanine nucleotide exchange factor ?Pix and the adaptor protein p66(Shc) are important players in Akt-independent inactivation of FOXO3a transcription factor.
34	16713446	CCK stimulated an association of Lyn with PKC-delta, Shc, p125(FAK) and PYK2 as well as with their autophosphorylated forms, but not with Cbl, p85, p130(CAS) or ERK 1/2.