PMID- 10080535
OWN - NLM
STAT- MEDLINE
DCOM- 19990401
LR  - 20190516
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 65
IP  - 3
DP  - 1999 Mar
TI  - Regulation of arachidonic acid release and cytosolic phospholipase A2 activation.
PG  - 330-6
AB  - 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.
FAU - Gijon, M A
AU  - Gijon MA
AD  - Department of Pediatrics, National Jewish Medical and Research Center, Denver,
      Colorado 80206, USA.
FAU - Leslie, C C
AU  - Leslie CC
LA  - eng
GR  - P01 HL034303/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - United States
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/*metabolism
MH  - Cell Membrane/*metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Macrophage Activation
MH  - Macrophages/metabolism
MH  - Mice
MH  - Phospholipases A/*metabolism
MH  - Phospholipases A2
RF  - 48
EDAT- 1999/03/18 00:00
MHDA- 1999/03/18 00:01
CRDT- 1999/03/18 00:00
PHST- 1999/03/18 00:00 [pubmed]
PHST- 1999/03/18 00:01 [medline]
PHST- 1999/03/18 00:00 [entrez]
AID - 10.1002/jlb.65.3.330 [doi]
PST - ppublish
SO  - J Leukoc Biol. 1999 Mar;65(3):330-6. doi: 10.1002/jlb.65.3.330.