Arch Virol (1997) 142: 953±964
Bovine papillomavirus E5 oncogene stimulates DNA synthesis
in C127 ®broblasts without general effects on growth factor
responsive protein phosphorylations
T. T. Wheeler*, M. K. O'Banion**, A. M. Colasurdo, and D. A. Young
Endocrine-Metabolism Unit, Department of Medicine, University of Rochester
Medical Center, Rochester, New York, U.S.A.
Accepted October 29, 1996
Summary. 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 in¯uence of E5 on the range
of receptor mediated changes in protein phosphorylation has not been
addressed. We looked for the in¯uence of E5 on DNA synthesis as well as
the phosphorylation of over 1000 cellular phosphoproteins in mouse C127
®broblasts and subclones harboring wild type (ID13)-, E5
(E6oCl) mutant BPVs. The cells containing E5 had an altered growth
response to fresh serum or PDGF but we observed no general in¯uences 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-speci®c in¯uence 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.
Papillomaviruses are a diverse group of DNA tumor viruses that are the
etiologic agents of benign epithelial tumors as well as some epithelial
malignancies (reviewed in [1, 11, 29]). The genetics of cellular transformation
by these viruses has been largely elucidated from studies of bovine
Present addresses: *Dairy Science Group, New Zealand Pastoral Agriculture Research
Institute, Hamilton, New Zealand; **Department of Neurobiology and Anatomy, University
of Rochester Medical Center, Rochester, NY, U.S.A.