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Complexes of focal adhesion kinase (FAK) and Crk-associated substrate (p130(Cas)) are elevated in cytoskeleton-associated fractions following adhesion and Src transformation. Requirements for Src kinase activity and FAK proline-rich motifs.

The focal adhesion kinase (FAK) and Crk-associated substrate, p130(Cas) (Cas), have been implicated in diverse signaling pathways including those mediated by integrins, G-protein-coupled receptors, tyrosine kinase receptors, and the v-src and v-crk oncogenes. The recent identification of a direct interaction between FAK and Cas prompted the examination of potential regulation of FAK.Cas complexes by factors that result in concomitant increase in their phosphotyrosine content, namely cell adhesion and transformation by Src. Both conditions resulted in elevated FAK.Cas complex levels in nonionic detergent-insoluble fractions, indicating increased association with the cytoskeleton. For activated Src, this effect requires an active Src catalytic domain but not its Src homology 2 (SH2) or Src homology 3 (SH3) domains. FAK kinase domain tyrosines 576 and 577 are also required, suggesting that direct phosphorylation of these sites by Src may influence the solubility and/or stability of the complex. FAK-Cas association was only observed in the context of Cas binding to at least one of two distinct proline-rich sites on FAK. These findings firmly establish a direct interaction between FAK and Cas and demonstrate that Src can influence the subcellular localization of the complex by a tyrosine phosphorylation-dependent mechanism.

Pubmed ID: 9038154

Authors

  • Polte TR
  • Hanks SK

Journal

The Journal of biological chemistry

Publication Data

February 28, 1997

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM49882

Mesh Terms

  • Animals
  • COS Cells
  • Cell Adhesion
  • Cell Adhesion Molecules
  • Cytoskeleton
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Mice
  • Mice, Inbred BALB C
  • Polyethylene Glycols
  • Proline
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-cbl
  • Receptor, Insulin
  • Subcellular Fractions
  • Tyrosine
  • Ubiquitin-Protein Ligases
  • src-Family Kinases