title: Vanadate-dependent FAK activation is accomplished by the sustained FAK Tyr-576/577 phosphorylation.
abstract: Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase implicated in cell-matrix interaction and integrin signaling. It is well established that Tyr-397 is the FAK autophosphorylation site and Tyr-407, -576/577, -861, and -925 are the sites on murine FAK that are mediated by Src family kinases. To study how FAK is regulated by tyrosine phosphatase(s), cells overexpressing chicken FAK are treated with sodium vanadate. Both the phosphotyrosine content and the enzymatic activity of FAK are increased in response to vanadate. Interestingly, sustained FAK Tyr-576/577 and -863 phosphorylations are detected in vanadate-treated FAK overexpressors and are dependent on FAK autophosphorylation. Further analysis of sodium vanadate-treated FAK overexpressors reveals that the enhanced FAK kinase activity parallels its elevated Tyr-576/577 phosphorylation. Thus, we conclude that Src-mediated FAK phosphorylation is regulated by a tyrosine phosphatase(s) and may be of physioligical significance.
authors.affiliation: Institute of Biochemistry, Chung Shan Medical and Dental College, Taichung, Taiwan, Republic of China.
authors.forename: M C
authors.initials: MC
authors.lastname: Maa
authors.forename: T H
authors.initials: TH
authors.lastname: Leu
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases; D010649:Phenylalanine / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000378:metabolism*; D019061:src-Family Kinases
chemical_list: D015815:Cell Adhesion Molecules; D014638:Vanadates; D014443:Tyrosine; D010649:Phenylalanine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases