Phosphorylation of focal adhesion kinase at Tyrosine 407 negatively regulates Ras transformation of fibroblasts.
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.
Jeon
Jihyun
J
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.
Lee
Hyangjin
H
Park
Haein
H
Lee
Jung-hyun
JH
Choi
Sojoong
S
Hwang
Jisun
J
Han
Inn-Oc
IO
Oh
Eok-Soo
ES
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*
D014443:Tyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018631:ras Proteins