Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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CHO Cells
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Calcimycin / pharmacology
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Calcium / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases
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Cell Line
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Cricetinae
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Cytosol / enzymology
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Enzyme Activation
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Kinetics
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Models, Biological
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Mutagenesis, Site-Directed
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Peptide Mapping
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Phospholipases A / genetics
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Phospholipases A / isolation & purification
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Phospholipases A / metabolism*
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Phospholipases A2
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Phosphopeptides / isolation & purification
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Phosphorylation
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Protein Kinase C / metabolism
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Protein Kinases / metabolism*
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Receptors, Platelet-Derived Growth Factor / physiology
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Recombinant Proteins / metabolism
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Serine
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Tetradecanoylphorbol Acetate / pharmacology
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Transfection
Substances
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Phosphopeptides
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Recombinant Proteins
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Calcimycin
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Serine
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Protein Kinases
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Receptors, Platelet-Derived Growth Factor
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Protein Kinase C
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Calcium-Calmodulin-Dependent Protein Kinases
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Phospholipases A
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Phospholipases A2
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Tetradecanoylphorbol Acetate
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Calcium