Possible v-Crk-induced transformation through activation of Src kinases.
p47gag-crk (v-Crk) encoded by avian sarcoma virus CT10, causes an elevation of tyrosine phosphorylation of several cellular proteins. The lack of a protein-tyrosine kinase domain in v-Crk suggests its co-operation with cellular protein-tyrosine kinase activity. We have shown that suppression of a certain fraction of c-Src activity by Csk may require the binding of Csk to tyrosine-phosphorylated paxillin. In this study, we detected co-immunoprecipitation of tyrosine-phosphorylated paxillin with v-Crk in CT10-transformed chicken embryo fibroblasts (CEF), and demonstrated that v-Crk binding to paxillin can inhibit Csk binding to paxillin. A phosphotyrosine peptide, which can inhibit v-Crk binding to paxillin, did not inhibit Csk binding to paxillin, suggesting that v-Crk and Csk bind to different tyrosine-phosphorylated sites in paxillin. We also found that the kinase activity of the endogenous c-Src in CEF is elevated severalfold after CT10-transformation. We therefore suggest that the competitive binding of overexpressed v-Crk affects an efficient interaction of Csk with tyrosine-phosphorylated paxillin in CT10-transformed CEF. This would result in a failure in the suppression of the kinase activities of a population of c-Src and other Src family protein-tyrosine kinases as well, and these kinases may then contribute to the phosphorylation of cellular proteins in CT10-transformed CEF.
Sabe
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Laboratory of Molecular Oncology, Rockefeller University, New York, New York 10021-6399, USA.
Shoelson
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Hanafusa
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D000595:Amino Acid Sequence; D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D050736:Oncogene Protein v-crk; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D013379:Substrate Specificity
D003598:Cytoskeletal Proteins; D050736:Oncogene Protein v-crk; D051419:Paxillin; D010750:Phosphoproteins; D015682:Retroviridae Proteins, Oncogenic; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)