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Characterization of two activated mutants of human pp60c-src that escape c-Src kinase regulation by distinct mechanisms

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dc.contributor.author Bjorge, J. D. en_US
dc.contributor.author Bellagamba, C. en_US
dc.contributor.author Cheng, H. C. en_US
dc.contributor.author Tanaka, A. en_US
dc.contributor.author Wang, J. H. en_US
dc.contributor.author Fujita, D. J. en_US
dc.date.accessioned 2006-06-22T14:16:32Z
dc.date.available 2006-06-22T14:16:32Z
dc.date.issued 1995-10 en_US
dc.identifier.citation J Biol Chem 270, 24222-8 (1995) en_US
dc.identifier.uri http://hdl.handle.net/1807.1/157
dc.description This article is hosted on a website external to the CBCRA Open Access Archive. Selecting “View/Open” below will launch the full-text article in another browser window.
dc.description.abstract Two activated transforming mutants of human pp60c-src were found to possess single point mutations within the regulatory carboxyl terminus (E527K in CY CST201) and the kinase domain (E381G in WO CST1), respectively, that do not directly interfere with either the regulatory c-Src kinase (CSK) phosphorylation site (Tyr530) or the SH2/3 domains. In vivo, both mutant proteins are hypophosphorylated on their carboxyl-terminal regulatory tyrosines and are hyperactive. In an in vitro Src kinase inactivation assay, both mutant Src proteins exhibited resistance to inactivation by CSK relative to wild-type Src. Under these in vitro conditions, E381G c-Src was found to be phosphorylated by CSK to wild-type levels, while E527K c-Src was not detectably phosphorylated. The ability of CSK to phosphorylate a carboxyl-terminal peptide modelled against E527K c-Src was also impaired, suggesting that CSK is unable to recognize E527K c-Src as an efficient substrate. In the case of E381G c-Src, examination of whether its SH2/3 domains were accessible to the carboxyl-terminal regulatory phosphotyrosine revealed a highly reduced ability of autophosphorylated E381G c-Src to bind to a synthetic phosphopeptide modelled from the SH2-binding region of polyoma middle-T antigen which binds to Src SH2 with high affinity. This suggests that the E381G c-Src mutation results in an altered or reduced accessibility of the SH2 domain of the autophosphorylated form of E381G c-Src and may represent a previously undescribed mode of Src activation. Further study of these and other Src mutants may offer additional new insights into the regulation of "Src family" kinases. en_US
dc.description.provenance Made available in DSpace on 2006-06-22T14:16:32Z (GMT). No. of bitstreams: 1 Bjorge.1995.24222.html: 415 bytes, checksum: 50ebedd5a1cace17caa5925b1998f335 (MD5) Previous issue date: 1995-10 en
dc.format.extent 415 bytes
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dc.language.iso en en_US
dc.publisher American Society for Biochemistry and Molecular Biology en_US
dc.relation.uri http://www.asbmb.org/ en_US
dc.title Characterization of two activated mutants of human pp60c-src that escape c-Src kinase regulation by distinct mechanisms en_US
dc.type Article en_US

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