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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Movement / drug effects
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Cell Movement / physiology*
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Cells, Cultured
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / physiology
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / enzymology
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Focal Adhesion Kinase 1
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Focal Adhesion Kinase 2
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Focal Adhesion Protein-Tyrosine Kinases
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Humans
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Integrins / metabolism*
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology*
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Mutagenesis / physiology
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Platelet-Derived Growth Factor / pharmacology*
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Platelet-Derived Growth Factor / physiology
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src-Family Kinases / metabolism
Substances
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Integrins
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Platelet-Derived Growth Factor
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Epidermal Growth Factor
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ErbB Receptors
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Protein-Tyrosine Kinases
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Receptors, Platelet-Derived Growth Factor
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Focal Adhesion Kinase 1
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Focal Adhesion Kinase 2
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Focal Adhesion Protein-Tyrosine Kinases
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PTK2 protein, human
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src-Family Kinases