Dissociation of platelet-derived growth factor (PDGF) receptor autophosphorylation from other PDGF-mediated second messenger events.
Activated p21ras alters the platelet-derived growth factor (PDGF) signal transduction pathway in fibroblasts by inhibiting autophosphorylation of the receptor as well as by inhibiting the induction of the growth-related genes c-myc, c-fos, and JE. To elucidate the cause and effect relationships between receptor autophosphorylation and other second messenger events in the PDGF signaling pathway we created revertants of v-ras transformed cells by two methods: 1) the use of cAMP analogues, and 2) the introduction of a gene, Krev-1, which has been reported previously to revert ras transformed cells to normal morphology. Analysis of the revertants shows that the PDGF-mediated tyrosine phosphorylation of the 180-kDa PDGF receptor remains inhibited; however, the PDGF-mediated activation of phospholipase C and the induction of the growth-related genes c-myc, c-fos, and JE have been restored. These data suggest the presence of parallel pathways for PDGF signal transduction which are not dependent on autophosphorylation of the PDGF receptor.
Quiñones
M A
MA
Brigham and Women's Hospital, Boston, Massachusetts.
Mundschau
L J
LJ
Rake
J B
JB
Faller
D V
DV
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics; D000242:Cyclic AMP / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D011905:Genes, ras; D051379:Mice; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D019000:Phosphotyrosine; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020668:rap GTP-Binding Proteins
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011956:Receptors, Cell Surface; D019000:Phosphotyrosine; D014443:Tyrosine; D004247:DNA; D000242:Cyclic AMP; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium