Open AccessRole of Protein Kinase Cα and Mitogen-Activated Protein Kinases in Endothelin-1-Stimulation of Cytosolic Phospholipase A2 in Iris Sphincter Smooth Muscle
Author(s) -
Ata A. AbdelLatif,
Shahid Husain,
Sardar Y.K. Yousufzai
Publication year - 2000
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200036051-00037
Subject(s) - protein kinase c , microbiology and biotechnology , protein kinase a , phosphorylation , kinase , phospholipase c , diacylglycerol kinase , mitogen activated protein kinase , p38 mitogen activated protein kinases , biology , mapk/erk pathway , signal transduction
We have investigated the roles of protein kinase C (PKC) and mitogen-activated protein kinases (MAPK) in the phosphorylation and activation of cytosolic phospholipase A2 (cPLA2) in endothelin-1- (ET-1) stimulated cat iris sphincter smooth muscle (CISM) cells. We found that in these cells both PKC and p38 MAP kinases play a critical role in ET-1-induced cPLA, phosphorylation and arachidonic acid (AA) release. Our findings indicate that stimulation of the endothelin-A- (ET(A)) receptor leads to: (1) activation of Gq protein which stimulates phospholipase C to hydrolyze the polyphosphoinositide PIP, into diacylglycerol (DAG) and inositol trisphosphate (IP3), the DAG may then activate PKC to phosphorylate and activate cPLA2; and (2) activation of Gi protein, which, through a series of kinases, leads to the stimulation of p38 MAPK and subsequently to phosphorylation and activation of cPLA2. The ability of the activated ET(A)-receptor, which is coupled to both Gq and Gi proteins, to recruit and activate this complex signal transduction mechanism remains to be clarified.