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Regulation of arachidonic acid release and cytosolic Phospholipase A 2 activation
Author(s) -
Gijón Miguel A.,
Leslie Christina C.
Publication year - 1999
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 - 10.1002/jlb.65.3.330
Subject(s) - okadaic acid , arachidonic acid , microbiology and biotechnology , biology , thapsigargin , phosphorylation , biochemistry , cytosol , calcium , calcium in biology , phospholipase a2 , intracellular , phosphatase , chemistry , organic chemistry , enzyme
The 85‐kDa cytosolic PLA 2 (CPLA 2 ) mediates agonist‐induced arachidonic acid release in many cell models, including mouse peritoneal macrophages. cPLA 2 is regulated by an increase in intracellular calcium, which binds to an amino‐ terminal C2 domain and induces its translocation to the nuclear envelope and endoplasmic reticulum. Phosphorylation of cPLA 2 on S505 by mitogen‐activated protein kinases (MAPK) also contributes to activation. In macrophages, zymosan induces a transient increase in intracellular calcium and activation of MAPK, which together fully activate cPLA 2 and synergistically promote arachidonic acid release. There are alternative pathways for regulating cPLA 2 in macrophages because PMA and okadaic acid induce arachidonic acid release without increasing calcium. The baculovirus expression system is a useful model to study cPLA 2 activation. Sf9 cells expressing cPLA 2 release arachidonic acid to either A23187 or okadaic acid. cPLA 2 is phosphorylated on multiple sites in Sf9 cells, and phosphorylation of S727 is preferentially induced by okadaic acid. However, the phosphorylation sites are non‐essential and only S505 phosphorylation partially contributes to cPLA 2 activation in this model. Although okadaic acid does not increase intracellular calcium in Sf9 cells, calcium binding by the C2 domain is necessary for arachidonic acid release. A23187 and okadaic acid activate cPLA 2 by different mechanisms, yet both induce translocation to the nuclear envelope in Sf9 cells. The results demonstrate that alternative regulatory pathways can lead to cPLA 2 activation and arachidonic acid release. J. Leukoc. Biol. 65: 330–336; 1999.