Evidence that the viral Ki-ras protein, but not the pp60v-src protein of ASV, stimulates proliferation through the PDGF receptor.
Protamine sulfate (PS), a specific blocker of PDGF action, inhibited the proliferative response of tsKSV-NRK cells to a reactivated, temperature-sensitive viral Ki-RAS protein, but it did not affect the proliferative response of tsASV-NRK cells to a reactivated pp60v-src protein kinase. The inhibition by PS of the proliferation response of tsKSV-NRK cells to reactivated Ki-RAS protein was overcome by serum growth factors, notably EGF, and concentrated serum-free conditioned medium from cultured NRK cells infected with wild-type KSV, but not by a combination of PDGF and insulin. These observations suggest that the viral Ki-RAS protein, but not pp60v-src, stimulates proliferation exclusively by inducing the host cells to produce PDGF or PDGF-like mitogenic factors.
Durkin
J P
JP
Cellular Oncology Group, National Research Council of Canada, Ottawa, Ontario.
Whitfield
J F
JF
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007700:Kinetics; D007708:Kirsten murine sarcoma virus / Q000201:enzymology / Q000235:genetics; D015688:Oncogene Protein pp60(v-src); D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011479:Protamines / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras); D011956:Receptors, Cell Surface / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D012191:Retroviridae Proteins / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D011479:Protamines; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D012191:Retroviridae Proteins; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D015688:Oncogene Protein pp60(v-src); D016283:Proto-Oncogene Proteins p21(ras)