FOCAL ADHESION KINASE TYROSINE-861 IS A MAJOR SITE OF PHOSPHORYLATIONBY SRC

Focal adhesion kinase (FAK) participates in signaling events induced h v diverse stimuli including integrin engagement, oncogenic transformat ion, and mitogenic neuropeptides. FAK's signaling function is regulate d by tyrosine phosphorylation. The major autophosphorylation site is t yrosine-397, which interacts with the Src homology 2 (SH2) domain of S rc-family Src-family kinases including Src and Fyn. Full activation of FAK appears to require additional phosphorylation by the associated S rc-family kinases. Previously identified Src sites include catalytic d omain tyrosines-576 and -577, important for maximal FAK kinase activit y, and tyrosine-925, which permits an SH2-mediated association with Gr b2. A full understanding of FAK-mediated signaling events will require the identification of all sites of tyrosine phosphorylation. Here we report that tyrosine 861 is that major Src site in the carboxyl-termin al domain of FAK. Phosphotyroslne-861 may function in additional inter actions between FAK and SH2-containing proteins. (C) 1996 Academic Pre ss, Inc.