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Alliance canadienne pour la recherche sur le cancer du sein
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Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines

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dc.contributor.author Bjorge, J. D. en_US
dc.contributor.author Pang, A. en_US
dc.contributor.author Fujita, D. J. en_US
dc.date.accessioned 2006-06-22T14:16:33Z
dc.date.available 2006-06-22T14:16:33Z
dc.date.issued 2000-12 en_US
dc.identifier.citation J Biol Chem 275, 41439-46 (2000) en_US
dc.identifier.uri http://hdl.handle.net/1807.1/159
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 c-Src tyrosine kinase activity is elevated in several types of human cancer, and this has been attributed to elevated c-Src expression levels, increased c-Src specific activity, and activating mutations in c-Src. We have found a number of human breast cancer cell lines with elevated c-Src specific activity that also possess elevated phosphatase activity directed against the carboxyl-terminal negative regulatory domain of Src family kinases. To identify this phosphatase, cell extracts from MDA-MB-435S cells were chromatographed and the fractions were assayed for phosphatase activity. Four peaks of phosphatase activity directed against the nonspecific substrate poly(Glu/Tyr) were detected. One peak also dephosphorylated a peptide modeled against the c-Src carboxyl-terminal negative regulatory domain and intact human c-Src. Immunoblotting and immunodepletion experiments identified the phosphatase as protein-tyrosine phosphatase 1B (PTP1B). Examination of several human breast cancer cell lines with increased c-Src activity showed elevated levels of PTP1B protein relative to normal control breast cells. In vitro c-Src reactivation experiments confirmed the ability of PTP1B to dephosphorylate and activate c-Src. In vivo overexpression of PTP1B in 293 cells caused a 2-fold increase of endogenous c-Src kinase activity. Our findings indicate that PTP1B is the primary protein-tyrosine phosphatase capable of dephosphorylating c-Src in several human breast cancer cell lines and suggests a regulatory role for PTP1B in the control of c-Src kinase activity. en_US
dc.description.provenance Made available in DSpace on 2006-06-22T14:16:33Z (GMT). No. of bitstreams: 1 Bjorge.2000.41439.html: 415 bytes, checksum: d339291a3c2a82327826b60ee3c7a0cb (MD5) Previous issue date: 2000-12 en
dc.format.extent 415 bytes
dc.format.mimetype text/html
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 Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines en_US
dc.type Article en_US

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