Stable association of pp60(src) and pp59(fyn) with the focal adhesion- associated protein tyrosine kinase, pp125(FAK)

B. S. Cobb, M. D. Schaller, T. H. Leu, J. T. Parsons

研究成果: Article同行評審

480 引文 斯高帕斯(Scopus)

摘要

Changes in cellular growth and dramatic alterations in cell morphology and adhesion are common features of cells transformed by oncogenic protein tyrosine kinases, such as pp60(src) and other members of the Src family. In this report, we present evidence for the stable association of two Src family kinases (pp60(src) and pp59(fyn)) with tyrosine-phosphorylated forms of a focal adhesion-associated protein tyrosine kinase, pp125(FAK). In Src- transformed chicken embryo cells, most of the pp125(FAK) was stably complexed with activated pp60(src) (e.g., pp60(527F)). The stable association of pp125(FAK) with pp60(527F) in vivo required the structural integrity of the Src SH2 domain. The association of pp60(527F) and pp125(FAK) could be reconstituted in vitro by incubation of normal cell extracts with glutathione S-transferase fusion proteins containing SH2 or SH3/SH2 domains of pp60(src). Furthermore, the association of isolated SH2 or SH3/SH2 domains with in vitro 32P-labeled pp125(FAK) protected the major site of pp125(FAK) autophosphorylation from digestion with a tyrosine phosphatase, indicating that the autophosphorylation site of pp125(FAK) participates in binding with Src. Immunoprecipitation of Src family kinases from extracts of normal chicken embryo cells revealed stable complexes of pp59(fyn) and tyrosine- phosphorylated pp125(FAK). These data provide evidence for a direct interaction between two cytoplasmic nonreceptor protein tyrosine kinases and suggest that Src may contribute to changes in pp125(FAK) regulation in transformed cells. Furthermore, pp125(FAK) may directly participate in the targeting of pp59(fyn) or possibly other Src family kinases to focal adhesions in normal cells.

原文English
頁(從 - 到)147-155
頁數9
期刊Molecular and Cellular Biology
14
發行號1
DOIs
出版狀態Published - 1994

All Science Journal Classification (ASJC) codes

  • 分子生物學
  • 細胞生物學

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