Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors.
Simian sarcoma virus-transformed NIH 3T3 (SSV-NIH 3T3) and SSV-NRK cells secrete a potent growth-promoting activity identical with the platelet-derived growth factor (PDGF) in mitogenic assays. The secreted activity is blocked by anti-PDGF antisera and competes with 125I-PDGF for receptor binding, suggesting that the secreted protein is the transforming protein of SSV, p28v-sis, or its processed product. Secreted p28v-sis appears to stimulate autocrine cell growth of SSV-transformed cells because anti-PDGF antisera block 3H-thymidine incorporation into growing SSV-NIH 3T3 and SSV-NRK cells. SSV-transformed cells have reduced numbers of high-affinity 125I-PDGF receptors; PDGF/p28v-sis receptor was purified from SSV-NIH 3T3 cells and retained active protein tyrosine kinase activity stimulated by PDGF. The rate of tumor growth in athymic nude mice injected with SSV-transformed cells was compared with levels of secreted growth factor activity. The rate of tumor growth in nude mice correlated directly with levels of p28v-sis secreted by SSV-transformed cells.
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D007668:Kidney; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D012190:Retroviridae / Q000235:genetics*; D012842:Sarcoma Virus, Woolly Monkey / Q000235:genetics*; D015291:Transforming Growth Factors; D014764:Viral Proteins / Q000235:genetics
D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D014764:Viral Proteins; D015291:Transforming Growth Factors; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor