FAK integrates growth-factor and integrin signals to promote cell migration

Nat Cell Biol. 2000 May;2(5):249-56. doi: 10.1038/35010517.


Here we show that cells lacking focal adhesion kinase (FAK) are refractory to motility signals from platelet-derived and epidermal growth factors (PDGF and EGF respectively), and that stable re-expression of FAK rescues these defects. FAK associates with activated PDGF- and EGF-receptor (PDGFR and EGFR) signalling complexes, and expression of the band-4.1-like domain at the FAK amino terminus is sufficient to mediate an interaction with activated EGFR. However, efficient EGF-stimulated cell migration also requires FAK to be targeted, by its carboxy-terminal domain, to sites of integrin-receptor clustering. Although the kinase activity of FAK is not needed to promote PDGF- or EGF-stimulated cell motility, kinase-inactive FAK is transphosphorylated at the indispensable Src-kinase-binding site, FAK Y397, after EGF stimulation of cells. Our results establish that FAK is an important receptor-proximal link between growth-factor-receptor and integrin signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / physiology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Focal Adhesion Kinase 1
  • Focal Adhesion Kinase 2
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Integrins / metabolism*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Mutagenesis / physiology
  • Platelet-Derived Growth Factor / pharmacology*
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Platelet-Derived Growth Factor / physiology
  • src-Family Kinases / metabolism


  • Integrins
  • Platelet-Derived Growth Factor
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • Focal Adhesion Kinase 1
  • Focal Adhesion Kinase 2
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • src-Family Kinases