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Mol. Cell. Biol., 02 1995, 954-963, Vol 15, No. 2
MB Calalb, TR Polte and SK Hanks
Focal adhesion kinase (FAK) is a widely expressed nonreceptor protein-
tyrosine kinase implicated in integrin-mediated signal transduction
pathways and in the process of oncogenic transformation by v-Src. Elevation
of FAK's phosphotyrosine content, following both cell adhesion to
extracellular matrix substrata and cell transformation by Rous sarcoma
virus, correlates directly with an increased kinase activity. To help
elucidate the role of FAK phosphorylation in signal transduction events, we
used a tryptic phosphopeptide mapping approach to identify tyrosine sites
of phosphorylation responsive to both cell adhesion and Src transformation.
We have identified four tyrosines, 397, 407, 576, and 577, which are
phosphorylated in mouse BALB/3T3 fibroblasts in an adhesion-dependent
manner. Tyrosine 397 has been previously recognized as the major site of
FAK autophosphorylation. Phosphorylation of tyrosines 407, 576, and 577,
which are previously unrecognized sites, is significantly elevated in the
presence of c-Src in vitro and v-Src in vivo. Tyrosines 576 and 577 lie
within catalytic subdomain VIII--a region recognized as a target for
phosphorylation- mediated regulation of protein kinase activity. We found
that maximal kinase activity of FAK immune complexes requires
phosphorylation of both tyrosines 576 and 577. Our results indicate that
phosphorylation of FAK by Src (or other Src family kinases) is an important
step in the formation of an active signaling complex.
Copyright © 1995, American Society for Microbiology
Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
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