Role of phosphatidylinositol kinase in PDGF receptor signal transduction.
The molecules with which the platelet-derived growth factor (PDGF) receptor interacts to elicit the biochemical reactions responsible for cell proliferation have not been identified. Antisera directed against specific PDGF receptor peptides coprecipitated a phosphatidylinositol (PI) kinase and the PDGF receptor. Immunoprecipitates from PDGF-stimulated cells contained 10 to 50 times as much PI kinase as those from unstimulated cells. Mutation of the PDGF receptor by deletion of its kinase insert region resulted in a receptor markedly less effective than the wild type in eliciting cell proliferation and defective in PDGF-stimulated PI kinase, but still capable of PDGF-induced receptor autophosphorylation and phosphoinositide hydrolysis. These data show that the PDGF receptor is physically associated with a PDGF-sensitive PI kinase that is distinct from tyrosine kinase and is not required for PDGF-induced PI hydrolysis. The finding that the mutant PDGF receptor missing the kinase insert domain elicited known early biochemical responses to PDGF, but did not associate with or regulate PI kinase, suggests a novel role for the receptor-associated PI kinase in the transmission of mitogenic signals.
Coughlin
S R
SR
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Escobedo
J A
JA
Williams
L T
LT
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002460:Cell Line; D002845:Chromatography; D006224:Cricetinae; D007118:Immunoassay; D007163:Immunosorbent Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D019000:Phosphotyrosine; D014443:Tyrosine; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor