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Vol. 10, Issue 10, 3489-3505, October 1999
¶ and
*Department of Cell Biology and Anatomy, University of North
Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; and
Tyrosine phosphorylation of focal adhesion kinase (FAK) creates a
high-affinity binding site for the src homology 2 domain of the Src
family of tyrosine kinases. Assembly of a complex between FAK and Src
kinases may serve to regulate the subcellular localization and the
enzymatic activity of members of the Src family of kinases. We show
that simultaneous overexpression of FAK and pp60c-src or
p59fyn results in the enhancement of the tyrosine
phosphorylation of a limited number of cellular substrates, including
paxillin. Under these conditions, tyrosine phosphorylation of paxillin
is largely cell adhesion dependent. FAK mutants defective for Src
binding or focal adhesion targeting fail to cooperate with
pp60c-src or p59fyn to induce paxillin
phosphorylation, whereas catalytically defective FAK mutants can direct
paxillin phosphorylation. The negative regulatory site of
pp60c-src is hypophosphorylated when in complex with FAK,
and coexpression with FAK leads to a redistribution of
pp60c-src from a diffuse cellular location to focal
adhesions. A FAK mutant defective for Src binding does not effectively
induce the translocation of pp60c-src to focal adhesions.
These results suggest that association with FAK can alter the
localization of Src kinases and that FAK functions to direct
phosphorylation of cellular substrates by recruitment of Src kinases.
Department of Microbiology, University of Virginia
School of Medicine, Charlottesville, Virginia 22908
Corresponding author. E-mail address:
crispy4{at}med.unc.edu.
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