 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
| Bradshaw JM, Mitaxov V, Waksman G | | Investigation of phosphotyrosine recognition by the SH2 domain of the Src
kinase. | | J Mol Biol 1999 Nov 5;293(4) : 971-85. | | PMID: 10543978 |
| Chang BY, Chiang M, Cartwright CA | | The interaction of Src and RACK1 is enhanced by activation of protein
kinase C and tyrosine phosphorylation of RACK1. | | J Biol Chem 2001 Jun 8;276(23) : 20346-56. | | PMID: 11279199 |
| Chang BY, Conroy KB, Machleder EM, Cartwright CA | | RACK1, a receptor for activated C kinase and a homolog of the beta subunit
of G proteins, inhibits activity of src tyrosine kinases and growth of NIH
3T3 cells. | | Mol Cell Biol 1998 Jun;18(6) : 3245-56. | | PMID: 9584165 |
| Fan G, Shumay E, Malbon CC, Wang H | | c-Src tyrosine kinase binds the beta 2-adrenergic receptor via
phospho-Tyr-350, phosphorylates G-protein-linked receptor kinase 2, and
mediates agonist-induced receptor desensitization. | | J Biol Chem 2001 Apr 20;276(16) : 13240-7. | | PMID: 11278940 |
| Kuriyan J, Cowburn D | | Modular peptide recognition domains in eukaryotic signaling. | | Annu Rev Biophys Biomol Struct 1997;26() : 259-88. | | PMID: 9241420 |
| Li Y, Kuwahara H, Ren J, Wen G, Kufe D | | The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1
carcinoma-associated antigen with GSK3 beta and beta-catenin. | | J Biol Chem 2001 Mar 2;276(9) : 6061-4. | | PMID: 11152665 |
| Lombardo CR, Consler TG, Kassel DB | | In vitro phosphorylation of the epidermal growth factor receptor
autophosphorylation domain by c-src: identification of phosphorylation
sites and c-src SH2 domain binding sites. | | Biochemistry 1995 Dec 19;34(50) : 16456-66. | | PMID: 8845374 |
| Pawson T, Gish GD, Nash P | | SH2 domains, interaction modules and cellular wiring. | | Trends Cell Biol 2001 Dec;11(12) : 504-11. | | PMID: 11719057 |
| Sierke SL, Longo GM, Koland JG | | Structural basis of interactions between epidermal growth factor receptor
and SH2 domain proteins. | | Biochem Biophys Res Commun 1993 Feb 26;191(1) : 45-54. | | PMID: 7680558 |
| 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 |
| Yaffe MB | | Phosphotyrosine-binding domains in signal transduction. | | Nat Rev Mol Cell Biol 2002 Mar;3(3) : 177-86. | | PMID: 11994738 |
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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Cellular Component |
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cytosol |
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Molecular Function |
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SH2-domain binding |
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