The E5 gene product of rhesus papillomavirus is an activator of endogenous Ras and phosphatidylinositol-3′-kinase in NIH 3T3 cells

Jyotsna Ghai, Ronald S. Ostrow, Jakub Tolar, Ronald C. Mcglennen, Todd D. Lemke, Diane Tobolt, Zhanjian "John" Liu, Anthony J. Faras

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

We examined the effect of two rhesus papillomavirus 1 (RhPV) oncogenes on cytokine-induced signal transduction pathways leading to the possible activation of Ras protein (p21ras) and phosphatidylinositol kinase. p21ras in both the activated (GTP-bound) and inactivated (GDP-bound) states were quantitated. NIH 3T3 cell lines expressing the RhPV 1 E5 gene or epidermal growth factor receptor cDNA had about a sixfold higher ratio of p21ras-bound GTP to p21ras-bound GDP as compared with parental NIH 3T3 cells or a cell line expressing the RhPV 1 E7 gene under normal culture conditions, yet expressed similar levels of p21ras. Quiescent cells had dramatically reduced levels of activated p21ras, except those containing RhPV 1 E7. Levels were restored by stimulation with epidermal growth factor or platelet-derived growth factor. Both epidermal growth factor and platelet-derived growth factor receptor of RhPV 1 E5- and E7-containing cells responded to cytokine stimulation. Endogenous phosphatidylinositol-3′-kinase was up-regulated in NIH 3T3 cells transformed with the ES genes of RhPV 1 and bovine papillomavirus 1. These results suggest that E5 genes of papillomaviruses play a major role in the regulation of transduction pathways.

Original languageEnglish (US)
Pages (from-to)12879-12884
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number23
StatePublished - Nov 12 1996
Externally publishedYes

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Keywords

  • GTP-binding protein
  • Receptors
  • Signal transduction

ASJC Scopus subject areas

  • General

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