title: Tyr-863 phosphorylation enhances focal adhesion kinase autophosphorylation at Tyr-397.
abstract: Tyr-397 phosphorylation is important for focal adhesion kinase (FAK)-mediated signalling. In vitro FAK immunocomplex kinase experiments demonstrated that both FAK Tyr-576/577 and Tyr-863 phosphorylation regulated FAK Tyr-397 phosphorylation. While the former increased the intermolecular transphosphorylation activity of FAK, the latter was crucial for its cis-phosphorylation. This observation was further supported by the reduced complex formation between Src and 3F-FAK (576F/577F/863F-FAK) as compared to that between Src and 576F/577F-FAK or Src and 863F-FAK. Regulation of cis- and transphosphorylation activities of FAK by such a differential tyrosyl phosphorylation mechanism is unprecedented. Furthermore, in fibronectin-stimulated cells, both Tyr-576/577 and Tyr-863 phosphorylation could enhance FAK Tyr-397 phosphorylation. This observation implies that integrin-mediated FAK Tyr-397 phosphorylation was also regulated through both FAK cis- and transphosphorylation mechanisms.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China. tzengleu@mail.ncku.edu.tw
authors.forename: Tzeng-Horng
authors.initials: TH
authors.lastname: Leu
authors.forename: Ming-Chei
authors.initials: MC
authors.lastname: Maa
mesh_terms: D000818:Animals; D002642:Chick Embryo; D005353:Fibronectins / Q000502:physiology; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D005353:Fibronectins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases