FAK mediates the inhibition of glioma cell migration by truncated 24 kDa FGF-2.
A truncated form of 24kDa FGF-2 consisting of 86 NH(2)-terminal amino acids (ATE+31) inhibits cell migration in vitro and tumor development and angiogenesis in vivo. Focal adhesion kinase (FAK) is phosphorylated on tyrosine and serine sites after cell stimulation by growth factors. This study examined the effect of ATE+31 on FAK phosphorylation in human glioma cells. FAK and Pyk phosphorylation were evaluated at serines known to be involved with cell migration. We demonstrated that ATE+31 at 3 x 10(-11)M decreases phosphorylation levels of Tyr(407)-FAK and Ser(732)-FAK in the presence of platelet-derived growth factor (PDGF), that ATE+31 in the presence of PDGF alters the distribution of FAK and other phosphotyrosine proteins in the adhesion contacts, and that ATE+31 in the presence of PDGF has no effect on the activation of Pyk2. These data suggest that the inhibition of cell migration by ATE+31 occurs via Tyr(407)-FAK and Ser(732)-FAK.
Lin
Amy H
AH
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, United States.
Eliceiri
Brian P
BP
Levin
Eugene G
EG
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D005910:Glioma / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D016222:Fibroblast Growth Factor 2; D019000:Phosphotyrosine; D014443:Tyrosine; D012694:Serine; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; C496050:PTK2 protein, human