title: Akt1 promotes focal adhesion disassembly and cell motility through phosphorylation of FAK in growth factor-stimulated cells.
abstract: The crosstalk between spatial adhesion signals and temporal soluble signals is key in regulating cellular responses such as cell migration. Here we show that soluble growth factors enhance integrin signaling through Akt phosphorylation of FAK at Ser695 and Thr700. PDGF treatment or overexpression of active Akt1 in fibroblasts increased autophosphorylation of FAK at Tyr397, an essential event for integrin turnover and cell migration. Phosphorylation-defective mutants of FAK (S695A and T700A) underwent autophosphorylation at Tyr397 and promoted cell migration in response to the integrin ligand fibronectin, but importantly, not in response to PDGF. This study has unveiled a novel function of Akt as an 'ignition kinase' of FAK in growth factor signaling and may shed light on the mechanism by which growth factors regulate integrin signaling.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Maiko.Higuchi@mpi-bn.mpg.de
authors.forename: Maiko
authors.initials: M
authors.lastname: Higuchi
authors.forename: Rina
authors.initials: R
authors.lastname: Kihara
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Okazaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
authors.forename: Shiro
authors.initials: S
authors.lastname: Suetsugu
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Gotoh
mesh_terms: D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000235:genetics; D002522:Chlorocebus aethiops; D005353:Fibronectins / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020239:Receptor Cross-Talk; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D005353:Fibronectins; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D051418:Focal Adhesion Kinase 2; D051057:Proto-Oncogene Proteins c-akt