title: Modulation of the SH2 binding specificity and kinase activity of Src by tyrosine phosphorylation within its SH2 domain.
abstract: The Src family of kinases are held in an inactive state by interaction of their SH2 domain with a C-terminal phosphotyrosine. Dephosphorylation of this site can reactivate Src; however, recent evidence suggests that activation can also occur without dephosphorylation. In this study, platelet-derived growth factor receptor phosphorylation of Src on Tyr-213 specifically blocked binding of its SH2 domain to a phosphopeptide corresponding to the C-terminal regulatory sequence, while binding to other sequences, such as the platelet-derived growth factor receptor or a peptide from the epidermal growth factor receptor, was unaffected. Consequently, Src was activated over 50-fold. This is the first demonstration of regulation of a SH2 domain specificity by post-translational modification and is likely to be a general mechanism for regulation of all Src-like kinases.
authors.affiliation: Pharmaceutical Research Division, Ciba-Geigy Limited, Basel, Switzerland.
authors.forename: D R
authors.initials: DR
authors.lastname: Stover
authors.forename: P
authors.initials: P
authors.lastname: Furet
authors.forename: N B
authors.initials: NB
authors.lastname: Lydon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000737:chemistry / Q000378:metabolism*; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000737:chemistry; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D018411:Spodoptera; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D010748:Phosphopeptides; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D015688:Oncogene Protein pp60(v-src)