Calcium-independent phospholipase A2 mediates CREB phosphorylation in double-stranded RNA-stimulated endothelial cells.
One of the products of a calcium-independent phospholipase A2 (iPLA2) attack of plasmenylcholine, lysoplasmenylcholine, has previously been shown to activate cAMP-dependent protein kinase (PKA). Because endothelial cells respond to some agonists in part by the activation of iPLA2, the present study was designed to determine whether double-stranded RNA (dsRNA), the primary activator of the antiviral response in endothelial cells, elicits cAMP response element binding protein (CREB) phosphorylation through a mechanism mediated by iPLA2. dsRNA stimulated CREB phosphorylation in bovine pulmonary artery endothelial cells that was inhibited by the iPLA2 inhibitor, bromoenol lactone, and the PKA inhibitor, H-89. Additionally, the product of iPLA2 hydrolysis of plasmenylcholine and lysoplasmenylcholine elicited CREB phosphorylation in bovine pulmonary endothelial cells. Taken together, the present studies suggest that dsRNA as well as other agonists of endothelial cells elicit signaling mechanisms that include in part CREB phosphorylation mediated by iPLA2.
Martinson
Bradley D
BD
Department of Biochemistry, St. Louis University, Health Sciences Center, St. Louis, MO 63104, USA.
Albert
Carolyn J
CJ
Corbett
John A
JA
Wysolmerski
Robert B
RB
Ford
David A
DA
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D054522:Group VI Phospholipases A2; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology; D011651:Pulmonary Artery; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D012330:RNA, Double-Stranded; C021215:lysoplasmalogens; C015482:protein kinase modulator; D017868:Cyclic AMP-Dependent Protein Kinases; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate; D011070:Poly I-C