HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 16, 11676-11686, April 20, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/16/11676    most recent M608458200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ghosh, M. Articles by Leslie, C. C. Search for Related Content PubMed PubMed Citation Articles by Ghosh, M. Articles by Leslie, C. C. Social Bookmarking                      What's this?

Function, Activity, and Membrane Targeting of Cytosolic Phospholipase A₂ in Mouse Lung Fibroblasts^*

Moumita Ghosh, Robyn Loper, Farideh Ghomashchi, Dawn E. Tucker, Joseph V. Bonventre^¶, Michael H. Gelb, and Christina C. Leslie^||1

From the Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, the Departments of Chemistry and Biochemistry, University of Washington, Seattle, Washington 98195, the ^¶Renal Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, and the ^||Departments of Pathology and Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045

Group IVA cytosolic phospholipase A₂ (cPLA₂) initiates eicosanoid production; however, this pathway is not completely ablated in cPLA₂^–/– lung fibroblasts stimulated with A23187 [GenBank] or serum. cPLA₂^+/+ fibroblasts preferentially released arachidonic acid, but A23187 [GenBank] -stimulated cPLA₂^–/– fibroblasts nonspecifically released multiple fatty acids. Arachidonic acid release from cPLA₂ ^–/– fibroblasts was inhibited by the cPLA₂ inhibitors pyrrolidine-2 (IC₅₀, 0.03 µM) and Wyeth-1 (IC₅₀, 0.1 µM), implicating another C2 domain-containing group IV PLA₂. cPLA₂ ^–/– fibroblasts contain cPLA₂ and cPLA₂ but not cPLA₂ or cPLA₂. Purified cPLA₂ exhibited much higher lysophospholipase and PLA₂ activity than cPLA₂ and was potently inhibited by pyrrolidine-2 and Wyeth-1, which did not inhibit cPLA₂. In contrast to cPLA₂, cPLA₂ expressed in Sf9 cells mediated A23187 [GenBank] -induced arachidonic acid release, which was inhibited by pyrrolidine-2 and Wyeth-1. cPLA₂ exhibits specific activity, inhibitor sensitivity, and low micromolar calcium dependence similar to cPLA₂ and has been identified as the PLA₂ responsible for calcium-induced fatty acid release and prostaglandin E₂ production from cPLA₂ ^–/– lung fibroblasts. In response to ionomycin, EGFP-cPLA₂ translocated to ruffles and dynamic vesicular structures, whereas EGFP-cPLA₂ translocated to the Golgi and endoplasmic reticulum, suggesting distinct mechanisms of regulation for the two enzymes.

Received for publication, September 4, 2006 , and in revised form, January 19, 2007.

^* This work was supported by National Institutes of Health Grants HL61378 and HL34303 (to C. C. L.) and HL50040 (to M. H. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Movie 1.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) DQ888308 [GenBank] and DQ904008 [GenBank] .

¹ To whom correspondence should be addressed: Dept. of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206. Tel.: 303-398-1214; Fax: 303-270-2155; E-mail: lesliec{at}njc.org.

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

This article has been cited by other articles:

				C. Yuan, R. S. Sidhu, D. V. Kuklev, Y. Kado, M. Wada, I. Song, and W. L. Smith Cyclooxygenase Allosterism, Fatty Acid-mediated Cross-talk between Monomers of Cyclooxygenase Homodimers J. Biol. Chem., April 10, 2009; 284(15): 10046 - 10055. [Abstract] [Full Text] [PDF]

				A. Gubern, J. Casas, M. Barcelo-Torns, D. Barneda, X. de la Rosa, R. Masgrau, F. Picatoste, J. Balsinde, M. A. Balboa, and E. Claro Group IVA Phospholipase A2 Is Necessary for the Biogenesis of Lipid Droplets J. Biol. Chem., October 10, 2008; 283(41): 27369 - 27382. [Abstract] [Full Text] [PDF]

				J. T. Green, S. K. Orr, and R. P. Bazinet The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids J. Lipid Res., May 1, 2008; 49(5): 939 - 944. [Abstract] [Full Text] [PDF]

				L. Cubells, S. V. de Muga, F. Tebar, J. V. Bonventre, J. Balsinde, A. Pol, T. Grewal, and C. Enrich Annexin A6-induced Inhibition of Cytoplasmic Phospholipase A2 Is Linked to Caveolin-1 Export from the Golgi J. Biol. Chem., April 11, 2008; 283(15): 10174 - 10183. [Abstract] [Full Text] [PDF]

				C. Graf, B. Zemann, P. Rovina, N. Urtz, A. Schanzer, R. Reuschel, D. Mechtcheriakova, M. Muller, E. Fischer, C. Reichel, et al. Neutropenia with Impaired Immune Response to Streptococcus pneumoniae in Ceramide Kinase-Deficient Mice J. Immunol., March 1, 2008; 180(5): 3457 - 3466. [Abstract] [Full Text] [PDF]

				M. Wada, C. J. DeLong, Y. H. Hong, C. J. Rieke, I. Song, R. S. Sidhu, C. Yuan, M. Warnock, A. H. Schmaier, C. Yokoyama, et al. Enzymes and Receptors of Prostaglandin Pathways with Arachidonic Acid-derived Versus Eicosapentaenoic Acid-derived Substrates and Products J. Biol. Chem., August 3, 2007; 282(31): 22254 - 22266. [Abstract] [Full Text] [PDF]