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Vol. 10, Issue 8, 2507-2518, August 1999

*Department of Cell Biology and Anatomy and
The focal adhesion kinase (FAK) is discretely localized to focal
adhesions via its C-terminal focal adhesion-targeting (FAT) sequence. FAK is regulated by integrin-dependent cell adhesion and can regulate tyrosine phosphorylation of downstream substrates, like paxillin. By the use of a mutational strategy, the regions of FAK
that are required for cell adhesion-dependent regulation and for
inducing tyrosine phosphorylation of paxillin were determined. The
results show that the FAT sequence was the single region of FAK that
was required for each function. Furthermore, the FAT sequence of FAK
was replaced with a focal adhesion-targeting sequence from vinculin,
and the resulting chimera exhibited cell adhesion-dependent tyrosine
phosphorylation and could induce paxillin phosphorylation like
wild-type FAK. These results suggest that subcellular localization is
the major determinant of FAK function.
Lineberger Comprehensive Cancer Center, University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Corresponding author. E-mail address:
crispy4{at}med.unc.edu.
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