Increasing molecular diversity of secreted phospholipases A(2) and their receptors and binding proteins

Secreted phospholipases A(2) (sPLA(2)s) form a large family of structurally related enzymes which are widespread in nature. Snake venoms are known for decades to contain a tremendous molecular diversity of sPLA(2)s which can exert a myriad of toxic and pharmacological effects. Recent studies indicat e that mammalian cells also express a variety of sPLA(2)s with ten distinct members identified so far, in addition to the various other intracellular PLA(2)s. Furthermore, scanning of nucleic acid databases fueled by the diff erent genome pi-ejects indicates that several sPLA(2)s are also present in invertebrate animals like Drosophila melanogaster as well as in plants. All of these sPLA(2)s catalyze the hydrolysis of glycerophospholipids at the s n-2 position to release free fatty acids and lysophospholipids, and thus co uld be important for the biosynthesis of biologically active lipid mediator s. However, the recent identification of a variety of membrane and soluble proteins that bind to sPLA(2)s suggests that the sPLA(2) enzymes could also function as high affinity ligands. So far, most of the binding data have b een accumulated with venom sPLA(2)s and group IB and IIA mammalian sPLA(2)s . Collectively, venom sPLA(2)s have been shown to bind to membrane and solu ble mammalian proteins of the C-type lectin superfamily (M-type sPLA(2) rec eptor and lung surfactant proteins), to pentraxin and reticulocalbin protei ns, to factor Xa and to N-type receptors. Venom sPLA(2)s also associate wit h three distinct types of sPLA(2) inhibitors purified from snake serum that belong to the C-type lectin superfamily, to the three-finger protein super family and to proteins containing leucine-rich repeats. On the other hand, mammalian group IB and IIA sPLA(2)s call bind to the M-type receptor, and g roup IIA sPLA(2)s call associate with lung surfactant proteins, factor Xa a nd proteoglycans including glypican and decorin, a mammalian protein contai ning a leucine-rich repeat. (C) 2000 Elsevier Science B.V, All rights reser ved.