Stimulation of phosphatidylinositol 3'-kinase association with foca adhesion kinase by platelet-derived growth factor.
We have previously described the stable association of the focal adhesion kinase (FAK) with phosphatidylinositol 3'-kinase (PI3K) in NIH 3T3 cells. This interaction was stimulated by cell adhesion in vivo and by autophosphorylation of recombinant FAK in vitro. In this report, we show that platelet-derived growth factor (PDGF) could also specifically stimulate this association in vivo. This stimulation is independent of cell adhesion or the integrity of the cytoskeleton, suggesting potentially different mechanisms by which the cell surface PDGF receptor and integrins regulate PI3K:FAK associations. We also found that this increased association in response to PDGF occurred in the membrane fractions, consistent with the recruitment of PI3K to the cell surface by the activated PDGF receptor. These results provide a novel mechanism of cross-talk between the signaling pathways initiated by PDGF and that initiated by integrins and raise the intriguing possibility that FAK might participate in some of the cellular effects of the growth factors in modulating cell morphology and migration.
Chen
H C
HC
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.
Guan
J L
JL
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000201:enzymology
D015815:Cell Adhesion Molecules; D010982:Platelet-Derived Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse