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Mol. Cell. Biol., 12 1995, 6506-6512, Vol 15, No. 12
Copyright © 1995, American Society for Microbiology

Association of the viral oncoprotein STP-C488 with cellular ras

JU Jung and RC Desrosiers
New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.

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.


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