title: Phosphorylation of focal adhesion kinase at Tyrosine 407 negatively regulates Ras transformation of fibroblasts.
abstract: Focal adhesion kinase (FAK) mediates signal transduction in response to multiple extracellular inputs, via tyrosine phosphorylation at specific residues. We recently reported that FAK Tyr-407 phosphorylation negatively regulates the enzymatic and biological activities of FAK, unlike phosphorylation of other tyrosine residues. In this study, we further investigated the effect of FAK Tyr-407 phosphorylation on cell transformation. We found that FAK Tyr-407 phosphorylation was lower in H-Ras transformed NIH3T3 and K-Ras transformed rat-2 fibroblasts than in the respective untransformed control cells. Consistently, FAK Tyr-407 phosphorylation was decreased in parallel with cell transformation in H-Ras-inducible NIH3T3 cells and increased during trichostatin A-induced detransformation of both K-Ras transformed rat-2 fibroblasts and H-Ras transformed NIH3T3 cells. In addition, overexpression of a phosphorylation-mimicking FAK Tyr-407 mutant inhibited morphological transformation of H-Ras-inducible NIH3T3 cells and inhibited invasion activity and anchorage-independent growth of H-Ras-transformed NIH3T3 cells. Taken together, these data strongly suggest that FAK Tyr-407 phosphorylation negatively regulates transformation of fibroblasts.
authors.affiliation: Department of Life Sciences, Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Daehyun-dong, Seodaemoon-Gu, Seoul 120-750, Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Jeon
authors.forename: Hyangjin
authors.initials: H
authors.lastname: Lee
authors.forename: Haein
authors.initials: H
authors.lastname: Park
authors.forename: Jung-hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Sojoong
authors.initials: S
authors.lastname: Choi
authors.forename: Jisun
authors.initials: J
authors.lastname: Hwang
authors.forename: Inn-Oc
authors.initials: IO
authors.lastname: Han
authors.forename: Eok-Soo
authors.initials: ES
authors.lastname: Oh
mesh_terms: D000818:Animals; D001665:Binding Sites; D018938:Caco-2 Cells; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005347:Fibroblasts; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D014443:Tyrosine / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D014443:Tyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018631:ras Proteins