J. Lipid Res. Please sign the JLR Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on December 1, 2007

Papers In Press, published online ahead of print September 21, 2007
J. Lipid Res., doi:10.1194/jlr.M700356-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M700356-JLR200v1
48/12/2701    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Subramanian, P.
Right arrow Articles by Chalfant, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Subramanian, P.
Right arrow Articles by Chalfant, C. E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Submitted on August 9, 2007
Revised on September 20, 2007
Accepted on September 20, 2007

Anionic lipids activate group IVA cytosolic phospholipase A2 via distinct and separate mechanisms

Preeti Subramanian, Mohsin Vora, Luciana B. Gentile, Robert V. Stahelin, and Charles E. Chalfant

Biochemistry, Virginia Commonwealth University, Richmond, VA 23298-0614

Corresponding Author: cechalfant{at}vcu.edu

Previously, ceramide-1-phosphate (C1P) and phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) were demonstrated to be potent and specific activators of cPLA2. In this study, we hypothesized that these anionic lipids functionally activated the enzyme by distinctly different mechanisms. Indeed, surface plasmon resonance and surface dilution kinetics demonstrated that C1P was a more potent effector than PI(4,5)P2 in lowering the dissociation constant of the cPLA2alpha/PC interaction and increasing the residence time of the enzyme on the vesicles/micelles. PI(4,5)P2, in contrast to C1P, decreased the Michaelis-Menten constant (kmB), increasing the catalytic efficiency of the enzyme. Furthermore, PI(4,5)P2 activated cPLA2alpha with a stoichiometry of 1:1 versus C1P at 2.4:1. Lastly, PI(4,5)P2, but not C1P, increased the penetration ability of cPLA2alpha into PC-rich membranes. Therefore, this study demonstrates two distinct mechanisms for the activation of cPLA2alpha by anionic lipids. First, C1P activates cPLA2alpha by increasing the residence time of the enzyme on membranes. Second, PI(4,5)P2 activates the enzyme by increasing catalytic efficiency through increased membrane penetration.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
J. E. Burke, Y.-H. Hsu, R. A. Deems, S. Li, V. L. Woods Jr., and E. A. Dennis
A Phospholipid Substrate Molecule Residing in the Membrane Surface Mediates Opening of the Lid Region in Group IVA Cytosolic Phospholipase A2
J. Biol. Chem., November 7, 2008; 283(45): 31227 - 31236.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Mashimo, T. Hirabayashi, T. Murayama, and T. Shimizu
Cytosolic PLA2{alpha} activation in Purkinje neurons and its role in AMPA-receptor trafficking
J. Cell Sci., September 15, 2008; 121(18): 3015 - 3024.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.