cPLA2 is phosphorylated and activated by MAP kinase.
Treatment of cells with agents that stimulate the release of arachidonic acid causes increased serine phosphorylation and activation of cytosolic phospholipase A2 (cPLA2). Here we report that cPLA2 is a substrate for mitogen-activated protein (MAP) kinase. Moreover, phosphorylation by MAP kinase increases the enzymatic activity of cPLA2. The site of cPLA2 phosphorylation by MAP kinase, Ser-505, is identical to the major site of cPLA2 phosphorylation observed in phorbol ester-treated cells. Replacement of Ser-505 with Ala resulted in a mutant cPLA2 that is not a substrate for MAP kinase and causes little or no enhanced agonist-stimulated arachidonate release from intact cells. Taken together, these data indicate that MAP kinase mediates, at least in part, the agonist-induced activation of cPLA2.
Genetics Institute, Small Molecule Drug Discovery Group, Cambridge, Massachusetts 02140.
L L
LL
Lin
M
M
Wartmann
A Y
AY
Lin
J L
JL
Knopf
A
A
Seth
R J
RJ
Davis
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D007700:Kinetics; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D010449:Peptide Mapping; D010741:Phospholipases A / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D054467:Phospholipases A2; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D010748:Phosphopeptides; D011994:Recombinant Proteins; D000001:Calcimycin; D012694:Serine; D011494:Protein Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium