SHC-Transforming Protein 1 (SHC1)

SHC; SHCA; p52SHC; p66; p66SHC; SHC-transforming protein 3; SHC-transforming protein A; Src homology 2 domain-containing-transforming protein C1

SPN	S180
HGNC	10840
MGI	98296
PubMed	19055724
RGD	620446
UniProt	P29353
Wiki	SHC1

The SHC gene encodes a signaling and transforming protein containing Src homology 2 and 3 (SH2 and SH3) domains. The SHC gene encodes 2 widely expressed overlapping proteins of 46 and 52 kD, both containing a C-terminal SH2 domain. Adjacent to the SH2 region is a glycine- and proline-rich region. The 2 proteins differ in their N terminals. SHC proteins are involved in mitogenic signal transduction and act by coupling growth factor receptors to the RAS signaling pathway. The protein encoded by the SHC1 gene is thought to act as an adaptor in many signal transduction pathways, for example, facilitating the activation of RAS proteins in response to a variety of factors. SHC proteins are rapidly associated with and phosphorylated by growth factor receptors with intrinsic tyrosine kinase activity.

Reference

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Cell 70:93-104(1992) [PubMed] [Europe PMC] [Abstract]

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EMBO J. 16:706-716(1997) [PubMed] [Europe PMC] [Abstract]

"Characterization of human SHC p66 cDNA and its processed pseudogene mapping to Xq12-q13.1."
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Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

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Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Direct interaction between Shc and the platelet-derived growth factor beta-receptor."
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"Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses."
Neuron 12:691-705(1994) [PubMed] [Europe PMC] [Abstract]

"Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor."
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"Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains."
J. Biol. Chem. 270:23258-23262(1995) [PubMed] [Europe PMC] [Abstract]

"Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain."
Mol. Cell. Biol. 15:2500-2508(1995) [PubMed] [Europe PMC] [Abstract]

"Cloning and characterization of human SHIP, the 145-kD inositol 5-phosphatase that associates with SHC after cytokine stimulation."
Blood 88:2833-2840(1996) [PubMed] [Europe PMC] [Abstract]

"The Shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (Y239/240) that mediate protein-protein interactions."
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"Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors."
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Mol. Cell. Biol. 17:1824-1831(1997) [PubMed] [Europe PMC] [Abstract]

"Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation."
Oncogene 15:7-15(1997) [PubMed] [Europe PMC] [Abstract]

"Growth factors and insulin stimulate tyrosine phosphorylation of the 51C/SHIP2 protein."
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"Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase."
Mol. Cell. Biol. 18:1622-1634(1998) [PubMed] [Europe PMC] [Abstract]

"Multiple Grb2-mediated integrin-stimulated signaling pathways to ERK2/mitogen-activated protein kinase: summation of both c-Src- and focal adhesion kinase-initiated tyrosine phosphorylation events."
Mol. Cell. Biol. 18:2571-2585(1998) [PubMed] [Europe PMC] [Abstract]

"A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP2) is constitutively tyrosine phosphorylated and associated with src homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor cells."
Blood 93:2707-2720(1999) [PubMed] [Europe PMC] [Abstract]

"Ligand discrimination in signaling through an ErbB4 receptor homodimer."
J. Biol. Chem. 275:19803-19807(2000) [PubMed] [Europe PMC] [Abstract]

"The Src homology 2 domain containing inositol 5-phosphatase SHIP2 is recruited to the epidermal growth factor (EGF) receptor and dephosphorylates phosphatidylinositol 3,4,5-trisphosphate in EGF-stimulated COS-7 cells."
J. Biol. Chem. 276:28348-28355(2001) [PubMed] [Europe PMC] [Abstract]

"Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples."
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"The p66Shc longevity gene is silenced through epigenetic modifications of an alternative promoter."
J. Biol. Chem. 277:22370-22376(2002) [PubMed] [Europe PMC] [Abstract]

"EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis."
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"Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells."
J. Biol. Chem. 279:13224-13233(2004) [PubMed] [Europe PMC] [Abstract]

"Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress."
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"A cryptic targeting signal induces isoform-specific localization of p46Shc to mitochondria."
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"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
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"Role of herpes simplex virus VP11/12 tyrosine-based motifs in binding and activation of the Src family kinase Lck and recruitment of p85, Grb2, and Shc."
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"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the SH2 domain from the adaptor protein SHC: a model for peptide binding based on X-ray and NMR data."
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"Structure and ligand recognition of the phosphotyrosine binding domain of Shc."
Nature 378:584-592(1995) [PubMed] [Europe PMC] [Abstract]

"Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor."
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