 Abstract
Src Homology 2 (SH2) domains are small modular domains found within a great number of proteins involved in different signaling pathways. They are able to bind specific motifs containing a phopshorylated tyrosine residue, propagating the signal downstream promoting protein-protein interaction and/or modifying enzymatic activities. Different families of SH2 domains may have different binding specifity, which is usually determined by few residues C-terminal with respect to the pY (positions +1, +2 and +3. Non-phosphorylated peptides do not bind to the SH2 domains. At least three different binding motifs are known: pYEEI (Src-family SH2 domains), pY[IV].[VILP] (SH-PTP2, phospholipase C-gamma), pY.[EN] (GRB2). The interaction between SH2 domains and their substrates is however dependent also to cooperative contacts of other surface regions.
Selected references
| Brooks SR, Li X, Volanakis EJ, Carter RH | | Systematic analysis of the role of CD19 cytoplasmic tyrosines in
enhancement of activation in Daudi human B cells: clustering of
phospholipase C and Vav and of Grb2 and Sos with different CD19 tyrosines. | | J Immunol 2000 Mar 15;164(6) : 3123-31. | | PMID: 10706702 |
| Colledge M, Froehner SC | | Tyrosine phosphorylation of nicotinic acetylcholine receptor mediates Grb2
binding. | | J Neurosci 1997 Jul 1;17(13) : 5038-45. | | PMID: 9185541 |
| Palka HL, Park M, Tonks NK | | Hepatocyte growth factor receptor tyrosine kinase met is a substrate of
the receptor protein-tyrosine phosphatase DEP-1. | | J Biol Chem 2003 Feb 21;278(8) : 5728-35. | | PMID: 12475979 |
| Pawson T, Gish GD, Nash P | | SH2 domains, interaction modules and cellular wiring. | | Trends Cell Biol 2001 Dec;11(12) : 504-11. | | PMID: 11719057 |
| Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, King F, Roberts T, Ratnofsky S, Lechleider RJ, et al. | | SH2 domains recognize specific phosphopeptide sequences. | | Cell 1993 Mar 12;72(5) : 767-78. | | PMID: 7680959 |
| Sorkin A, McClure M, Huang F, Carter R | | Interaction of EGF receptor and grb2 in living cells visualized by
fluorescence resonance energy transfer (FRET) microscopy. | | Curr Biol 2000 Nov 2;10(21) : 1395-8. | | PMID: 11084343 |
| Stein E, Cerretti DP, Daniel TO | | Ligand activation of ELK receptor tyrosine kinase promotes its association
with Grb10 and Grb2 in vascular endothelial cells. | | J Biol Chem 1996 Sep 20;271(38) : 23588-93. | | PMID: 8798570 |
| Yaffe MB | | Phosphotyrosine-binding domains in signal transduction. | | Nat Rev Mol Cell Biol 2002 Mar;3(3) : 177-86. | | PMID: 11994738 |
| Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE | | Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated
LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen
receptor-mediated signaling. | | J Biol Chem 2000 Jul 28;275(30) : 23355-61. | | PMID: 10811803 |
| van der Geer P, Hunter T | | Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding
site, abrogates signal transduction by the murine CSF-1 receptor expressed
in Rat-2 fibroblasts. | | EMBO J 1993 Dec 15;12(13) : 5161-72. | | PMID: 8262059 |
This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.
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Biological Process |
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cell proliferation
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signal transduction
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transmembrane receptor protein tyrosine kinase signalimg pathway
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Cellular Component |
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cytosol |
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Molecular Function |
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SH2-domain binding |
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transmembrane receptor protein tyrosine kinase docking protein |
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