Phosphatidylinositol 3-kinase activity is required for the activation process of focal adhesion kinase by platelet-derived growth factor.
Platelet-derived growth factor (PDGF) is one of the agents which stimulate increase in phosphotyrosine content of focal adhesion kinase (FAK) in cultured cells. In the present study we report that wortmannin, a highly specific and potent inhibitor of the catalytic subunit of mammalian phosphatidylinositol (PI) 3-kinase, completely abolishes PDGF-BB-mediated increase in tyrosine phosphorylation of FAK in human umbilical vein smooth muscle cells. Furthermore, analysis of the wild-type and mutant human PDGF beta-receptors stably expressed in porcine aortic endothelial cells also demonstrates that the Y740/751F mutant receptor, which cannot interact with PI 3-kinase due to the mutational alteration of its binding sites for PI 3-kinase, fails to increase FAK phosphorylation after PDGF-BB stimulation. These data suggest the requirement for PI 3-kinase activity in the activation process of FAK downstream of the PDGF receptor.
Saito
Y
Y
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Mori
S
S
Yokote
K
K
Kanzaki
T
T
Saito
Y
Y
Morisaki
N
N
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D000077214:Becaplermin; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013552:Swine; D014162:Transfection; D000077191:Wortmannin
D000730:Androstadienes; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D000077191:Wortmannin