Human papillomavirus type 6b virus-like particles are able to activate the Ras-MAP kinase pathway and induce cell proliferation

Payne, Elizabeth, Bowles, Mark R., Don, Alistair, Hancock, John F. and McMillan, Nigel A. J. (2001) Human papillomavirus type 6b virus-like particles are able to activate the Ras-MAP kinase pathway and induce cell proliferation. Journal of Virology, 75 9: 4150-4157. doi:10.1128/JVI.75.9.4150-4157.2001


Author Payne, Elizabeth
Bowles, Mark R.
Don, Alistair
Hancock, John F.
McMillan, Nigel A. J.
Title Human papillomavirus type 6b virus-like particles are able to activate the Ras-MAP kinase pathway and induce cell proliferation
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 2001-05
Year available 2001
Sub-type Article (original research)
DOI 10.1128/JVI.75.9.4150-4157.2001
Open Access Status DOI
Volume 75
Issue 9
Start page 4150
End page 4157
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2001
Language eng
Subject C1
320402 Medical Virology
730108 Cancer and related disorders
321015 Oncology and Carcinogenesis
Abstract The initial step in viral infection is the attachment of the virus to the host cell via an interaction with its receptor. We have previously shown that a receptor for human papillomavirus is the alpha6 integrin. The alpha6 integrin is involved in the attachment of epithelial cells with the basement membrane, but recent evidence suggests that ligation of many integrins results in intracellular signaling events that influence cell proliferation. sere we present evidence that exposure of A431 human epithelial cells to human papillomavirus type 6b L1 virus-like particles (VLPs) results in a dose-dependent increase in cell proliferation, as measured by bromodeoxyuridine incorporation. This proliferation is Lost if VLPs are first denatured or incubated with a monoclonal antibody against L1 protein. The MEK1 inhibitor PB98059 inhibits the VLP-mediated increase in fell proliferation, suggesting involvement of the Ras-MAP kinase pathway, Indeed, VLP binding results in rapid phosphorylation of the beta4 integrin upon tyrosine residues and subsequent recruitment of the adapter protein She to beta4, Within 30 min, the activation of Ras, Raf, and Erk2 was observed. Finally, the upregulation of c-myc mRNA was observed at 60 min, These data indicate that human papillomavirus type 6b is able to signal cells via the Ras-MAP kinase pathway to induce cell proliferation. We hypothesize that such a mechanism would allow papillomaviruses to infect hosts more successfully by increasing the potential pool of cells they are able to infect via the initiation of proliferation in resting keratinocyte stem and suprabasal cells.
Keyword Virology
Alpha(6)beta(4) Integrin
Cytoplasmic Domain
Protein-kinase
Signal-transduction
Receptors
Adhesion
Binding
Growth
Phosphorylation
Identification
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 25 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 14 Aug 2007, 15:31:22 EST