Cloning and expression of a membrane receptor for secretory phospholipases A2.
Snake venom and mammalian secretory phospholipases A2 are structurally related enzymes that have been associated with several toxic (neurotoxicity, myotoxicity, etc.), pathological (inflammation, hypersensitivity, etc.), or physiological (contraction, proliferation, etc.) processes. We have previously shown that snake venom PLA2s have specific high affinity receptors. Here, we report the molecular cloning of one of these 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 domain, and a intracellular C-terminal domain. The 1458-residue PLA2 receptor, expressed in transfected cells, binds svPLA2 with very high affinities (Kd values approximately 10-20 pM). It also tightly binds the two structural types of msPLA2s, i.e. pancreatic PLA2 and synovial PLA2 (Kd approximately 1-10 nM). This receptor might have a key role in normal and pathological actions of secretory PLA2s.
Lambeau
G
G
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Ancian
P
P
Barhanin
J
J
Lazdunski
M
M
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D004546:Elapid Venoms / Q000378:metabolism; D015870:Gene Expression; D007700:Kinetics; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D010179:Pancreas / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D017433:Protein Structure, Secondary; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D054507:Receptors, Phospholipase A2; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D030162:Reptilian Proteins; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014162:Transfection
D002352:Carrier Proteins; D018076:DNA, Complementary; D004546:Elapid Venoms; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D011994:Recombinant Proteins; D030162:Reptilian Proteins; D010741:Phospholipases A; C073206:Oxyuranus scutellatus toxin 2; D054467:Phospholipases A2