Linked Life Data

8777586

Source:http://linkedlifedata.com/resource/pubmed/id/8777586

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1996-9-19
pubmed:abstractText
To summarize the regulation of cPLA2, we have proposed a model for the activation of cPLA2 based both on our previous studies (Clark et al., 1991; Lin et al., 1993) and the work of many others (Fig. 5). In this model, cPLA2 is tightly regulated by multiple pathways, including those that control Ca2+ concentration, phosphorylation states and cPLA2 protein levels, to exert both rapid and prolonged effects on cellular processes, such as inflammation. cPLA2 is rapidly activated by increased intracellular Ca2+ concentration and phosphorylation by MAP kinase. When cells are stimulated with a ligand for a receptor, such as ATP or PDGF, PLC is activated via either a G protein-dependent or -independent process, leading to the production of diacylglycerol (DAG) and inositol triphosphate (IP3). The rise in these intracellular messengers cause the activation of PKC and mobilization of intracellular Ca2+. Alternatively, the increase in intracellular Ca2+ can result from a Ca2+ influx. Increased Ca2+ acts through the CaLB domain to cause translocation of cPLA2 from the cytosol to the membrane where its substrate, phospholipid, is localized. This step is essential for the activation of cPLA2 and may account for the partial activation of cPLA2 in the absence of phosphorylation. MAP kinase activation can occur through both PKC-dependent and -independent mechanisms (Cobb et al., 1991; Posada and Cooper, 1992; Qiu and Leslie, 1994). In many cases, this pathway is also G protein-dependent. Activated MAP kinase phosphorylates cPLA2 at Ser-505, causing increased enzymatic activity of cPLA2, which is realized only upon translocation of cPLA2 to the membrane. Therefore, full activation of cPLA2 requires both increased cytosolic Ca2+ and cPLA2 phosphorylation at Ser-505. In a more delayed response, cPLA2 activity in the cells can be controlled by changes in its expression levels, such as in response to inflammatory cytokines and certain growth factors. Thus the expression level of cPLA2 is regulated by both transcriptional and post-transcriptional mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0929-7855
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
83-117
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Cytosolic phospholipase A2.
pubmed:affiliation
Small Molecule Drug Discovery Group, Genetics Institute, Cambridge, MA 0214, USA.
pubmed:publicationType
Journal Article, Review