Association of the viral oncoprotein STP-C488 with cellular ras.
The STP-C488 oncogene of herpesvirus saimiri has transforming activity independent of the rest of the viral genome. We now demonstrate that STP-C488 associates with cellular ras in transformed cells. Mutations that disrupted this association with ras disrupted the transforming ability of the STP-C488 oncogene. Binding assays showed that STP-C488 was capable of competing with raf-1 for binding to ras. Expression of STP-C488 activated the ras signaling pathway as evidenced by a two- to fourfold increase in the ratio of ras-GTP to ras-GDP and by the constitutive activation of mitogen-activated protein kinase. Consistent with an activation of signaling through ras, STP-C488 expression induced ras-dependent neurite outgrowth in PC12 cells. STP-C488 is the first virus-encoded protein shown to achieve oncogenic transformation via association with cellular ras.
New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
J U
JU
Jung
R C
RC
Desrosiers
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002522:Chlorocebus aethiops; D005822:Genetic Vectors; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure; D009856:Oncogene Proteins, Viral / Q000302:isolation & purification / Q000378:metabolism*; D009857:Oncogenes; D016716:PC12 Cells; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D015183:Restriction Mapping; D012190:Retroviridae; D015398:Signal Transduction; D014162:Transfection; D018631:ras Proteins / Q000302:isolation & purification / Q000378:metabolism*
D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; C072817:STP-C488 protein, Herpesvirus saimiri; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins