학술논문
The E5 Gene Product of Rhesus Papillomavirus is an Activator of Endogenous Ras and phosphatidylinositol-3 ′ -kinase in NIH 3T3 Cells
Document Type
research-article
Author
Source
Proceedings of the National Academy of Sciences of the United States of America, 1996 Nov 01. 93(23), 12879-12884.
Subject
Language
English
ISSN
00278424
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 (p21 ras ) and phosphatidylinositol kinase. p21 ras 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 p21 ras -bound GTP to p21 ras -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 p21 ras . Quiescent cells had dramatically reduced levels of activated p21 ras , except those containing RhPV 1 E7. Levels were restored by stimulation with epidermal growth factor and 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 E5 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.