Premium
Regulation of cytosolic phospholipase A 2 α by hsp90 and a p54 kinase in okadaic acid‐stimulated macrophages
Author(s) -
Tucker Dawn E.,
Gijón Miguel A.,
Spencer Diane M.,
Qiu ZhiHua,
Gelb Michael H.,
Leslie Christina C.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0308197
Subject(s) - geldanamycin , hsp90 , biology , protein kinase c , okadaic acid , phospholipase a2 , arachidonic acid , phospholipase a , zymosan , kinase , cytosol , phospholipase , heat shock protein , protein kinase a , biochemistry , phosphorylation , microbiology and biotechnology , phosphatase , enzyme , gene , in vitro
In resident mouse peritoneal macrophages, group IVA cytosolic phospholipase A 2 (cPLA 2 α) mediates arachidonic acid (AA) release and eicosanoid production in response to diverse agonists such as A23187, phorbol myristate acetate, zymosan, and the enterotoxin, okadaic acid (OA). cPLA 2 α is regulated by phosphorylation and by calcium that binds to the C2 domain and induces translocation from the cytosol to membranes. In contrast, OA activates cPLA 2 α‐induced AA release and translocation to the Golgi in macrophages without an apparent increase in calcium. Inhibitors of heat shock protein 90 (hsp90), geldanamycin, and herbimycin blocked AA release in response to OA but not to A23187, PMA, or zymosan. OA, but not the other agonists, induced activation of a cytosolic serine/threonine 54‐kDa kinase (p54), which phosphorylated cPLA 2 α in in‐gel kinase assays and was associated with cPLA 2 α in immunoprecipitates. Activation of the p54 kinase was inhibited by geldanamycin. The kinase coimmunoprecipitated with hsp90 in unstimulated macrophages, and OA induced its loss from hsp90, concomitant with its association with cPLA 2 α. The results demonstrate a role for hsp90 in regulating cPLA 2 α‐mediated AA release that involves association of a p54 kinase with cPLA 2 α upon OA stimulation.