Papillomavirus virus-like particles activate the PI3-kinase pathway via alpha-6 beta-4 integrin upon binding

Fothergill, Thomas and McMillan, Nigel A. J. (2006) Papillomavirus virus-like particles activate the PI3-kinase pathway via alpha-6 beta-4 integrin upon binding. Virology, 352 2: 319-328. doi:10.1016/j.virol.2006.05.002


Author Fothergill, Thomas
McMillan, Nigel A. J.
Title Papillomavirus virus-like particles activate the PI3-kinase pathway via alpha-6 beta-4 integrin upon binding
Journal name Virology   Check publisher's open access policy
ISSN 0042-6822
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1016/j.virol.2006.05.002
Volume 352
Issue 2
Start page 319
End page 328
Total pages 10
Place of publication San Diego, California
Publisher Elsevier
Language eng
Subject C1
321015 Oncology and Carcinogenesis
730108 Cancer and related disorders
060506 Virology
Abstract We have previously shown that human papillomavirus virus-like particles (VLPs) are able to activate the Ras/MAP kinase pathway. Ras can also elicit an anti-apoptotic signal via PI3-kinase so we investigated this further. Here we show that binding of VLPs from HPV types 6b, 18, 3 1, 35 and BPV1 results in activation of PI3-kinase. Activation was achieved by either L1 or L1/L2 VLPs and was dependent on both VLP-cell interaction and correct conformation of the virus particle. VLP-induced PI3-kinase activity resulted in efficient downstream signaling to Akt and consequent phosphorylation of FKHR and GSK3 beta. We also present evidence that PV signaling is activated via the alpha 6 beta 4 integrin. These data suggest that papillomaviruses use a common receptor that is able to signal through to Ras. Combined activation of the Ras/MAP kinase and PI3-kinase pathways may be beneficial for the virus by increasing cell numbers and producing an environment more conducive to infection. (c) 2006 Elsevier Inc. All rights reserved
Keyword Papillomavirus
Integrin
VLP
PI3-kinase
Akt
Virology
Protein-kinase-b
Nf-kappa-b
Cell-surface
Signaling Pathway
Heparan-sulfate
Phosphatidylinositol 3-kinase
Immunodeficiency-virus
Human Keratinocytes
Viral Replication
Alpha(6) Integrin
FKHR
GSK3β
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 19:04:31 EST