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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-6-7
pubmed:abstractText
Cytosolic group IV phospholipase A2 (cPLA2) is a ubiquitously expressed enzyme with key roles in intracellular signaling. The current paradigm for activation of cPLA2 by stimuli proposes that both an increase in intracellular calcium and mitogen-activated protein kinase-mediated phosphorylation occur together to fully activate the enzyme. Calcium is currently thought to be needed for translocation of the cPLA2 to the membrane via a C2 domain, whereas the role of cPLA2 phosphorylation is less clearly defined. Herein, we report that brief exposure of P388D1 macrophages to UV radiation results in a rapid, cPLA2-mediated arachidonic acid mobilization, without increases in intracellular calcium. Thus, increased Ca2+ availability is a dispensable signal for cPLA2 activation, which suggests the existence of alternative mechanisms for the enzyme to efficiently interact with membranes. Our previous in vitro data suggested the importance of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) in the association of cPLA2 to model membranes and hence in the regulation of cPLA2 activity. Experiments described herein show that PtdInsP2 also serves a similar role in vivo. Moreover, inhibition of PtdInsP2 formation during activation conditions leads to inhibition of the cPLA2-mediated arachidonic acid mobilization. These results suggest that cellular PtdInsP2 levels are involved in the regulation of group IV cPLA2 activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5398-402
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10799904-Animals, pubmed-meshheading:10799904-Arachidonic Acid, pubmed-meshheading:10799904-Calcium Signaling, pubmed-meshheading:10799904-Cell Membrane, pubmed-meshheading:10799904-Cell Membrane Permeability, pubmed-meshheading:10799904-Cytosol, pubmed-meshheading:10799904-Enzyme Activation, pubmed-meshheading:10799904-Leukemia P388, pubmed-meshheading:10799904-Lipopolysaccharides, pubmed-meshheading:10799904-Macrophages, pubmed-meshheading:10799904-Mice, pubmed-meshheading:10799904-Phosphatidylinositol 4,5-Diphosphate, pubmed-meshheading:10799904-Phospholipases A, pubmed-meshheading:10799904-Phospholipases A2, pubmed-meshheading:10799904-Platelet Activating Factor, pubmed-meshheading:10799904-Protein Kinase C, pubmed-meshheading:10799904-Proto-Oncogene Proteins c-raf, pubmed-meshheading:10799904-Tumor Cells, Cultured, pubmed-meshheading:10799904-Ultraviolet Rays
pubmed:year
2000
pubmed:articleTitle
Cellular regulation of cytosolic group IV phospholipase A2 by phosphatidylinositol bisphosphate levels.
pubmed:affiliation
Department of Chemistry, University of California at San Diego, La Jolla, CA 92093, USA. jbalsinde@ucsd.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.