ANTIIDIOTYPIC MONOCLONAL-ANTIBODY RECOGNIZES A CONSENSUS RECOGNITION SITE FOR PHOSPHATIDYLSERINE IN PHOSPHATIDYLSERINE-SPECIFIC MONOCLONAL-ANTIBODY AND PROTEIN-KINASE-C

In order to elucidate the molecular mechanisms responsible for the spe cific lipid-protein interactions, we have undertaken structural and id iotypic analyses of a monoclonal antibody, PS4A7, which binds specific ally to phosphatidylserine (PS). Here we showed that one of the anti-i diotypic monoclonal antibodies raised against PS4A7 cross-reacted exte nsively with protein kinase C (PKC) and inhibited the activation of th e enzymatic activity. The binding of the anti-idiotypic antibody to PK C was inhibited specifically by PS, but not by other phospholipids inc luding 1,2-diacyl-sn-glycero-3 -phospho-D-serine or 1,2-diacyl-sn-glyc ero-3 -phospho-L-homoserine. In contrast, the binding of the anti-idio typic mAb to the enzyme was significantly enhanced in the presence of either diacylglycerol or sphingosine. These findings indicate that the PS-specific monoclonal antibody and PKC share a consensus structure w hich is responsible for the specific interaction with PS and both diac ylglycerol and sphingosine may induce a similar conformational change which exposes the PS-specific binding site of the enzyme.