title: Focal adhesion kinase tyrosine-861 is a major site of phosphorylation by Src.
abstract: Focal adhesion kinase (FAK) participates in signaling events induced by diverse stimuli including integrin engagement, oncogenic transformation and mitogenic neuropeptides. FAK's signaling function is regulated by tyrosine phosphorylation. The major autophosphorylation site is tyrosine-397, which interacts with the Src homology 2 (SH2) domain of Src-family kinases including Src and Fyn. Full activation of FAK appears to require additional phosphorylation by the associated Src-family kinases. Previously identified Src sites include catalytic domain tyrosines-576 and -577, important for maximal FAK kinase activity, and tyrosine-925, which permits an SH2-mediated association with Grb2. 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 the major Src site in the carboxyl-terminal domain of FAK. Phosphotyrosine-861 may function in additional interactions between FAK and SH2-containing proteins.
authors.affiliation: Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Calalb
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: T R
authors.initials: TR
authors.lastname: Polte
authors.forename: S K
authors.initials: SK
authors.lastname: Hanks
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D015815:Cell Adhesion Molecules; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse