Valentin E, Lambeau G
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560, Valbonne, France.
Biochim Biophys Acta. 2000 Oct 31;1488(1-2):59-70. doi: 10.1016/s1388-1981(00)00110-4.
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 indicate 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 different genome projects 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 sn-2 position to release free fatty acids and lysophospholipids, and thus could be important for the biosynthesis of biologically active lipid mediators. 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 been 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 soluble mammalian proteins of the C-type lectin superfamily (M-type sPLA(2) receptor and lung surfactant proteins), to pentraxin and reticulocalbin proteins, to factor Xa and to N-type receptors. Venom sPLA(2)s also associate with three distinct types of sPLA(2) inhibitors purified from snake serum that belong to the C-type lectin superfamily, to the three-finger protein superfamily and to proteins containing leucine-rich repeats. On the other hand, mammalian group IB and IIA sPLA(2)s can bind to the M-type receptor, and group IIA sPLA(2)s can associate with lung surfactant proteins, factor Xa and proteoglycans including glypican and decorin, a mammalian protein containing a leucine-rich repeat.
分泌型磷脂酶A2（sPLA2）构成了一个结构相关酶的大家族，广泛存在于自然界。几十年来，人们已知蛇毒中含有种类繁多的sPLA2，它们可产生无数的毒性和药理作用。最近的研究表明，除了各种其他细胞内磷脂酶A2外，哺乳动物细胞也表达多种sPLA2，目前已鉴定出十个不同的成员。此外，由不同基因组计划推动的核酸数据库扫描表明，果蝇等无脊椎动物以及植物中也存在几种sPLA2。所有这些sPLA2都催化甘油磷脂在sn-2位的水解，释放游离脂肪酸和溶血磷脂，因此可能对生物活性脂质介质的生物合成很重要。然而，最近鉴定出的多种与sPLA2结合的膜蛋白和可溶性蛋白表明，sPLA2酶也可能作为高亲和力配体发挥作用。到目前为止，大多数结合数据是关于蛇毒sPLA2以及IB组和IIA组哺乳动物sPLA2积累的。总的来说，蛇毒sPLA2已被证明可与C型凝集素超家族的膜蛋白和可溶性哺乳动物蛋白（M型sPLA2受体和肺表面活性物质蛋白）、五聚素和网钙蛋白、因子Xa以及N型受体结合。蛇毒sPLA2还与从蛇血清中纯化的三种不同类型的sPLA2抑制剂相关联，这些抑制剂分别属于C型凝集素超家族、三指蛋白超家族以及含有富含亮氨酸重复序列的蛋白。另一方面，哺乳动物IB组和IIA组sPLA2可与M型受体结合，IIA组sPLA2可与肺表面活性物质蛋白、因子Xa以及蛋白聚糖（包括磷脂酰肌醇蛋白聚糖和核心蛋白聚糖）结合，后者是一种含有富含亮氨酸重复序列的哺乳动物蛋白。
