Bovine papillomavirus E5 oncogene stimulates DNA synthesis in C127 fibroblasts without general effects on growth...

The bovine papillomavirus (BPV) transforming gene E5 is thought to modulate growth factor receptor function leading to a stimulation of growth factor signal transduction pathways. However, the influence of E5 on the range of receptor mediated changes in protein phosphorylation has not been addressed. We looked for the influence of E5 on DNA synthesis as well as the phosphorylation of over 1000 cellular phosphoproteins in mouse C127 fibroblasts and subclones harboring wild type (ID13)-, E5- mutant (XL3-2), and E6- (E6oCl) mutant BPVs. The cells containing E5 had an altered growth response to fresh serum or PDGF but we observed no general influences of E5 transformation on sets of serum-, phorbol ester-, and PDGF-responsive phosphoproteins, comprising 25, 18, and 16 overlapping members, respectively. Indeed, most of the phosphoproteins comprising these sets remain equally responsive to these growth factors in all four cell lines. The only evidence of an E5-specific influence on protein phosphorylation was with 4 phosphoproteins, two whose PDGF-responsiveness was abolished and two with abolished serum-, phorbol ester- and PDGF-responsiveness. Thus E5 modulates only a subset of the cascade of receptor-mediated downstream protein phosphorylations.