p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

doi:10.1074/jbc.272.27.17145

p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A₂*

From the Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892

Abstract

Using a two hybrid system screen of a human cDNA library, we have found that p11, a unique member of the S100 family of calcium-binding proteins, interacts with the carboxyl region of the 85-kDa cytosolic phospholipase A₂(cPLA₂). p11 synthesized in a cell-free system interacts with cPLA₂ in vitro. The p11-cPLA₂complex is detectable from a human bronchial epithelial cell line (BEAS 2B). Furthermore, p11 inhibits cPLA₂ activity in vitro. Selective inhibition of p11 expression in the BEAS 2B cells by antisense RNA results in an increased PLA₂activity as well as an increased release of prelabeled arachidonic acid. This study demonstrates a novel mechanism for the regulation of cPLA₂ by an S100 protein.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵‡ To whom correspondence should be addressed: Critical Care Medicine Dept., Bldg. 10, Rm. 7D43, National Institutes of Health, Bethesda, MD 20892. Tel.: 301-402-4846; Fax: 301-480-3389.
↵1 The abbreviations used are: PLA₂, phospholipase A₂; cPLA₂, cytosolic phospholipase A₂; AA, arachidonic acid; X-Gal, 5-bromo-4-chloro-3-indolyl-β-d-galactoside; bp, base pair; HPLC, high pressure liquid chromatography; PAGE, polyacrylamide gel electrophoresis; HBSS, Hanks’ balanced salt solution.
- Received February 14, 1997.
- Revision received April 23, 1997.