Article abstract
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. Schlaepfer1
Abstract
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.
- Department of Immunology, IMM 26, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
- These authors contributed equally to this work
- Department of Stomatology, University of California San Francisco, San Francisco, California 94143, USA
- QCB-A Division of BioSource International, Hopkinton, Massachusetts 01748, USA
Correspondence to: David D. Schlaepfer1 e-mail: dschlaep@scripps.edu
