Nature Cell Biology
2, 249 - 256 (2000)
Published online: 27 March 2000; | doi:10.1038/35010517
FAK integrates growth-factor and integrin signals to promote cell migration
David J. Sieg1, 2, Christof R. Hauck1, 2, Dusko Ilic3, Candice K. Klingbeil1, Erik Schaefer4, Caroline H. Damsky3
& David D. Schlaepfer11
Department of Immunology, IMM 26, The Scripps Research Institute,
10550 N. Torrey Pines Road, La Jolla, California 92037, USA 2
These authors contributed equally to this work 3
Department of Stomatology, University of California San
Francisco, San Francisco, California 94143, USA 4
QCB-A Division of BioSource International, Hopkinton, Massachusetts
01748, USA
Correspondence should be addressed to David D. Schlaepfer dschlaep@scripps.eduHere 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.
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