Pancreatic-type phospholipase A2 activates prostaglandin E2 production in rat mesangial cells by receptor binding reaction.
Our earlier studies have shown that mammalian pancreatic group I phospholipase A2 (PLA2-I) has its specific receptor (PLA2 receptor) on a wide range of mammalian cells and that the receptor-binding capability of PLA2-I is a property of this molecule separable from its enzymatic activity. To clarify whether PLA2 activity is required for eliciting a biological response via the receptor or not, we examined the enzymatic activity of PLA2-I/PLA2 receptor complex and the inducibility of prostaglandin (PG) E2 production in rat mesangial cells by mutant PLA2s-I. Using a recombinant soluble PLA2 receptor, we first found that PLA2-I could not hydrolyze a phospholipid substrate when complexed with the receptor. In the next experiment using various mutant porcine PLA2s-I, we found that PGE2 production in rat mesangial cells could be induced by a mutant PLA2-I which retained the receptor-binding activity but had almost completely lost its enzymatic activity. These findings indicate that the enzyme action of PLA2-I is not required for a PLA2-I-induced biological response, i.e., the augmentation of PGE2 production in rat mesangial cells.
Kishino
J
J
Shionogi Research Laboratories, Shionogi & Company, Ltd., Osaka.
Kawamoto
K
K
Ishizaki
J
J
Verheij
H M
HM
Ohara
O
O
Arita
H
H
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D015232:Dinoprostone / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005920:Glomerular Mesangium / Q000378:metabolism*; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D010179:Pancreas / Q000201:enzymology*; D010741:Phospholipases A / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D054467:Phospholipases A2; D017354:Point Mutation; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D054507:Receptors, Phospholipase A2; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine; D014162:Transfection
D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D011994:Recombinant Proteins; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone