CLONING AND EXPRESSION OF A MEMBRANE-RECEPTOR FOR SECRETORY PHOSPHOLIPASES-A(2)

Snake venom and mammalian secretory phospholipases A2 are structurally related enzymes that have been associated with several toxic (neuroto xicity, myotoxicity, etc.), pathological (inflammation, hypersensitivi ty, etc.), or physiological (contraction, proliferation, etc.) process es. We have previously shown that snake venom PLA2s have specific high affinity receptors. Here, we report the molecular cloning of one of t hese PLA2 receptors (molecular mass approximately 180 kDa), previously purified from rabbit skeletal muscle. It is a membrane protein with a N-terminal cysteine-rich domain, a fibronectin type II domain, eight repeats of a carbohydrate recognition domain, a unique transmembrane d omain, and an intracellular C-terminal domain. The 1458-residue PLA2 r eceptor, expressed in transfected cells, binds svPLA2 with very high a ffinities (K(d) values approximately 10-20 pM). It also tightly binds the two structural types of msPLA2s, i.e. pancreatic PLA2 and synovial PLA2 (K(d) approximately 1-10 nM). This receptor might have a key rol e in normal and pathological actions of secretory PLA2s.