Open AccessThe E5 gene product of rhesus papillomavirus is an activator of endogenous Ras and phosphatidylinositol-3′-kinase in NIH 3T3 cells
Author(s) -
Jyotsna Ghai,
Ronald S. Ostrow,
Jakub Tolar,
Ronald C. McGlennen,
Todd D. Lemke,
Diane Tobolt,
Zhanjiang Liu,
Anthony J. Faras
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.23.12879
Subject(s) - phosphatidylinositol , epidermal growth factor , biology , tgf alpha , 3t3 cells , activator (genetics) , signal transduction , microbiology and biotechnology , growth factor , growth factor receptor , cytokine , kinase , cell culture , epidermal growth factor receptor , receptor , transfection , immunology , biochemistry , genetics
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 1E5 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 1E7 gene under normal culture conditions, yet expressed similar levels of p21ras . Quiescent cells had dramatically reduced levels of activated p21ras , except those containing RhPV 1E7 . 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 1E5 - andE7 -containing cells responded to cytokine stimulation. Endogenous phosphatidylinositol-3′-kinase was up-regulated in NIH 3T3 cells transformed with theE5 genes of RhPV 1 and bovine papillomavirus 1. These results suggest thatE5 genes of papillomaviruses play a major role in the regulation of transduction pathways.