Selective inhibition of human group IIA-secreted phospholipase a 2 (hGIIA) signaling reveals arachidonic acid metabolism is associated with colocalization of hGIIA to vimentin in rheumatoid synoviocytes

Lee, Lawrence K., Bryant, Katherine J., Bouveret, Romaric, Lei, Pei-Wen, Duff, Anthony P., Harrop, Stephen J., Huang, Edwin P., Harvey, Richard P., Gelb, Michael H., Gray, Peter P., Curmi, Paul M., Cunningham, Anne M., Church, W. Bret and Scott, Kieran F. (2013) Selective inhibition of human group IIA-secreted phospholipase a 2 (hGIIA) signaling reveals arachidonic acid metabolism is associated with colocalization of hGIIA to vimentin in rheumatoid synoviocytes. Journal of Biological Chemistry, 288 21: 15269-15279. doi:10.1074/jbc.M112.397893

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ320732_OA.pdf Full text (open access) application/pdf 8.53MB 0

Author Lee, Lawrence K.
Bryant, Katherine J.
Bouveret, Romaric
Lei, Pei-Wen
Duff, Anthony P.
Harrop, Stephen J.
Huang, Edwin P.
Harvey, Richard P.
Gelb, Michael H.
Gray, Peter P.
Curmi, Paul M.
Cunningham, Anne M.
Church, W. Bret
Scott, Kieran F.
Title Selective inhibition of human group IIA-secreted phospholipase a 2 (hGIIA) signaling reveals arachidonic acid metabolism is associated with colocalization of hGIIA to vimentin in rheumatoid synoviocytes
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2013-05-24
Sub-type Article (original research)
DOI 10.1074/jbc.M112.397893
Open Access Status File (Publisher version)
Volume 288
Issue 21
Start page 15269
End page 15279
Total pages 11
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2014
Language eng
Subject 1307 Cell Biology
1312 Molecular Biology
Abstract Human group IIA secreted phospholipase A2 (hGIIA) promotes tumor growth and inflammation and can act independently of its well described catalytic lipase activity via an alternative poorly understood signaling pathway. With six chemically diverse inhibitors we show that it is possible to selectively inhibit hGIIA signaling over catalysis, and x-ray crystal structures illustrate that signaling involves a pharmacologically distinct surface to the catalytic site.Wedemonstrate in rheumatoid fibroblast-like synoviocytes that non-catalytic signaling is associated with rapid internalization of the enzyme and colocalization with vimentin. Trafficking of exogenous hGIIA was monitored with immunofluorescence studies, which revealed that vimentin localization is disrupted by inhibitors of signaling that belong to a rare class of small molecule inhibitors that modulate protein-protein interactions. This study provides structural and pharmacological evidence for an association between vimentin, hGIIA, and arachidonic acid metabolism in synovial inflammation, avenues for selective interrogation of hGIIA signaling, and new strategies for therapeutic hGIIA inhibitor design.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Australian Institute for Bioengineering and Nanotechnology Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 13 Jan 2014, 14:55:50 EST by Anthony Yeates on behalf of Aust Institute for Bioengineering & Nanotechnology