PDGF beta-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complex.
Platelet-derived growth factor (PDGF) stimulated the tyrosine phosphorylation of the GTPase activating protein (GAP) in 3T3 cells and in CHO cells expressing wild-type PDGF receptors, but not in several CHO cell lines expressing mutant receptors defective in transmitting mitogenic signals. Following PDGF treatment of cells, GAP physically associated with the PDGF receptor and with Raf-1, phospholipase c-gamma, and PI-3 kinase, suggesting that PDGF induced the formation of complexes of signaling molecules. The association of GAP with the PDGF receptor and the phosphorylation of GAP with the PDGF receptor and the phosphorylation of GAP were reconstituted in vitro using purified protein and in insect cells expressing murine PDGF receptor and human GAP. However, in cells transformed by activated c-Ha-ras, which are defective in certain responses to PDGF, GAP failed to associate with the PDGF receptor or increase its phosphotyrosine content in response to PDGF. The association of GAP with ligand-activated PDGF receptors may directly link PDGF and ras signaling pathways.
Kaplan
D R
DR
Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco.
Morrison
D K
DK
Wong
G
G
McCormick
F
F
Williams
L T
LT
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D020690:GTPase-Activating Proteins; D011905:Genes, ras; D046911:Macromolecular Substances; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D015398:Signal Transduction; D014443:Tyrosine; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D011956:Receptors, Cell Surface; D020703:ras GTPase-Activating Proteins; D014443:Tyrosine; D011494:Protein Kinases; D017479:Receptors, Platelet-Derived Growth Factor