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

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.
Mesh Terms:
Cell Movement, Cells, Cultured, Epidermal Growth Factor, Fibroblasts, Focal Adhesion Kinase 1, Focal Adhesion Kinase 2, Focal Adhesion Protein-Tyrosine Kinases, Humans, Integrins, MAP Kinase Signaling System, Mutagenesis, Platelet-Derived Growth Factor, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Receptor, Epidermal Growth Factor, Receptors, Platelet-Derived Growth Factor, src-Family Kinases
Nat. Cell Biol.
Date: May. 01, 2000
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