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.