Platelet-derived growth factor induces phosphatidylinositol 3-kinase release from the middle T-pp60c-src complex and association with the platelet-derived growth factor receptor.
Both platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce mitogenesis in normal rat kidney (NRK) fibroblasts transformed by the polyoma virus middle T (pmt) oncogene. In unstimulated pmt-NRK cells phosphatidylinositol 3-kinase forms a complex with the middle T protein and pp60c-src. PDGF treatment causes a release of phosphatidylinositol 3-kinase activity from the complex and a simultaneous increase in activity associated with the PDGF receptor. In contrast after treatment with EGF the majority of phosphatidylinositol 3-kinase activity remains associated with the middle T-pp60c-src complex. Proliferation of NRK fibroblasts transformed by the v-src oncogene is already maximal, and no further stimulation is observed with either PDGF or EGF. Neither growth factor induces dissociation of the complex between phosphatidylinositol 3-kinase and pp60v-src. These observations suggest that the complex between phosphatidylinositol 3-kinase, the middle T protein and pp60c-src is dissociable, and that phosphatidylinositol 3-kinase plays different roles in mitogenic signal transduction by the PDGF and EGF receptors.
Zhang
Q X
QX
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia.
Baldwin
G S
GS
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000302:isolation & purification / Q000378:metabolism*; D000077214:Becaplermin; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000302:isolation & purification / Q000378:metabolism; D007668:Kidney; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000302:isolation & purification / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D000952:Antigens, Polyomavirus Transforming; D008565:Membrane Proteins; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D016392:Proto-Oncogene Proteins pp60(c-src)