title: Focal adhesion kinase is negatively regulated by phosphorylation at tyrosine 407.
abstract: Focal adhesion kinase (FAK) mediates signal transduction in response to multiple extracellular inputs via tyrosine phosphorylation at specific residues. Although several tyrosine phosphorylation events have been linked to FAK activation and downstream signal transduction, the function of FAK phosphorylation at Tyr(407) was previously unknown. Here, we show for the first time that phosphorylation of FAK Tyr(407) increases during serum starvation, contact inhibition, and cell cycle arrest, all conditions under which activating FAK Tyr(397) phosphorylation decreases. Transfection of NIH3T3 cells with a phosphorylation-mimicking FAK 407E mutant decreased autophosphorylation at Tyr(397) and inhibited both FAK kinase activity in vitro and FAK-mediated functions such as cell adhesion, spreading, proliferation, and migration. The opposite effects were observed in cells transfected with nonphosphorylatable mutant FAK 407F. Taken together, these data suggest the novel concept that FAK Tyr(407) phosphorylation negatively regulates the enzymatic and biological activities of FAK.
authors.affiliation: Department of Life Sciences, Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul 120-750.
authors.forename: Yangmi
authors.initials: Y
authors.lastname: Lim
authors.forename: Haein
authors.initials: H
authors.lastname: Park
authors.forename: Jihyun
authors.initials: J
authors.lastname: Jeon
authors.forename: Innoc
authors.initials: I
authors.lastname: Han
authors.forename: Jinsook
authors.initials: J
authors.lastname: Kim
authors.forename: Eek-Hoon
authors.initials: EH
authors.lastname: Jho
authors.forename: Eok-Soo
authors.initials: ES
authors.lastname: Oh
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D004789:Enzyme Activation / Q000235:genetics; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
chemical_list: D014443:Tyrosine; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse