Phosphorylation of focal adhesion kinase at Tyrosine 407 negatively regulates Ras transformation of fibroblasts

Biochem Biophys Res Commun. 2007 Dec 28;364(4):1062-6. doi: 10.1016/j.bbrc.2007.10.134. Epub 2007 Oct 30.


Focal adhesion kinase (FAK) mediates signal transduction in response to multiple extracellular inputs, via tyrosine phosphorylation at specific residues. We recently reported that FAK Tyr-407 phosphorylation negatively regulates the enzymatic and biological activities of FAK, unlike phosphorylation of other tyrosine residues. In this study, we further investigated the effect of FAK Tyr-407 phosphorylation on cell transformation. We found that FAK Tyr-407 phosphorylation was lower in H-Ras transformed NIH3T3 and K-Ras transformed rat-2 fibroblasts than in the respective untransformed control cells. Consistently, FAK Tyr-407 phosphorylation was decreased in parallel with cell transformation in H-Ras-inducible NIH3T3 cells and increased during trichostatin A-induced detransformation of both K-Ras transformed rat-2 fibroblasts and H-Ras transformed NIH3T3 cells. In addition, overexpression of a phosphorylation-mimicking FAK Tyr-407 mutant inhibited morphological transformation of H-Ras-inducible NIH3T3 cells and inhibited invasion activity and anchorage-independent growth of H-Ras-transformed NIH3T3 cells. Taken together, these data strongly suggest that FAK Tyr-407 phosphorylation negatively regulates transformation of fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Caco-2 Cells
  • Cell Line
  • Cell Transformation, Neoplastic / metabolism*
  • Fibroblasts
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Phosphorylation
  • Protein Binding
  • Rats
  • Tyrosine / metabolism*
  • ras Proteins / metabolism*


  • Tyrosine
  • Focal Adhesion Protein-Tyrosine Kinases
  • ras Proteins