/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/10080535.csml - 2009.07.01.10:37

Original Literature	Model OverView
Publication Title Regulation of arachidonic acid release and cytosolic phospholipase A2activation. Authors Gijon MA, Leslie CC. Affiliation Department of Pediatrics, National Jewish Medical and Research Center, Denver,Colorado 80206, USA. Abstract The 85-kDa cytosolic PLA2 (cPLA2) mediates agonist-induced arachidonic acidrelease in many cell models, including mouse peritoneal macrophages. cPLA2 isregulated by an increase in intracellular calcium, which binds to anamino-terminal C2 domain and induces its translocation to the nuclear envelopeand endoplasmic reticulum. Phosphorylation of cPLA2 on S505 by mitogen-activatedprotein kinases (MAPK) also contributes to activation. In macrophages, zymosaninduces a transient increase in intracellular calcium and activation of MAPK,which together fully activate cPLA2 and synergistically promote arachidonic acidrelease. There are alternative pathways for regulating cPLA2 in macrophagesbecause PMA and okadaic acid induce arachidonic acid release without increasingcalcium. The baculovirus expression system is a useful model to study cPLA2activation. Sf9 cells expressing cPLA2 release arachidonic acid to either A23187or okadaic acid. cPLA2 is phosphorylated on multiple sites in Sf9 cells, andphosphorylation of S727 is preferentially induced by okadaic acid. However, thephosphorylation sites are non-essential and only S505 phosphorylation partiallycontributes to cPLA2 activation in this model. Although okadaic acid does notincrease intracellular calcium in Sf9 cells, calcium binding by the C2 domain isnecessary for arachidonic acid release. A23187 and okadaic acid activate cPLA2by different mechanisms, yet both induce translocation to the nuclear envelopein Sf9 cells. The results demonstrate that alternative regulatory pathways canlead to cPLA2 activation and arachidonic acid release. PMID 10080535

Original Literature	Model OverView
Publication: J Leukoc Biol. 1999 Mar;65(3):330-6. Title: Regulation of arachidonic acid release and cytosolic phospholipase A2 activation. Authors: Gijon MA, Leslie CC. Affiliation: Department of Pediatrics, National Jewish Medical and Research Center, Denver,Colorado 80206, USA. Abstract: The 85-kDa cytosolic PLA2 (cPLA2) mediates agonist-induced arachidonic acid release in many cell models, including mouse peritoneal macrophages. cPLA2 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 cPLA2 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 cPLA2 and synergistically promote arachidonic acid release. There are alternative pathways for regulating cPLA2 in macrophages because PMA and okadaic acid induce arachidonic acid release without increasing calcium. The baculovirus expression system is a useful model to study cPLA2 activation. Sf9 cells expressing cPLA2 release arachidonic acid to either A23187 or okadaic acid. cPLA2 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 cPLA2 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 cPLA2 by different mechanisms, yet both induce translocation to the nuclear envelope in Sf9 cells. The results demonstrate that alternative regulatory pathways can lead to cPLA2 activation and arachidonic acid release. PMID:

The 85-kDa cytosolic PLA2 (cPLA2) mediates agonist-induced arachidonic acid release in many cell models, including mouse peritoneal macrophages. cPLA2 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 cPLA2 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 cPLA2 and synergistically promote arachidonic acid release. There are alternative pathways for regulating cPLA2 in macrophages because PMA and okadaic acid induce arachidonic acid release without increasing calcium. The baculovirus expression system is a useful model to study cPLA2 activation. Sf9 cells expressing cPLA2 release arachidonic acid to either A23187 or okadaic acid. cPLA2 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 cPLA2 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 cPLA2 by different mechanisms, yet both induce translocation to the nuclear envelope in Sf9 cells. The results demonstrate that alternative regulatory pathways can lead to cPLA2 activation and arachidonic acid release.

Model Detail

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