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 (PDG F and EGF respectively), and that stable re-expression of FAK rescues these defects. FAK associates with activated PDGF- and EGF-receptor (PDGFR and E GFR) signalling complexes, and expression of the band-4.1-like domain at th e FAK amino terminus is sufficient to mediate an interaction with activated EGFR. However, efficient EGF-stimulated cell migration also requires FAK t o be targeted, by its carboxy-terminal domain, to sites of integrin-recepto r clustering. Although the kinase activity of FAK is not needed to promote PDGF- or EGF-stimulated cell motility, kinase-inactive FAK is transphosphor ylated at the indispensable Src-kinase-binding site, FAK Y397, after EGF st imulation of cells. Our results establish that FAK is an important receptor -proximal link between growth-factor-receptor and integrin signalling pathw ays.