Cupillard L, Mulherkar R, Gomez N, Kadam S, Valentin E, Lazdunski M, Lambeau G
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
J Biol Chem. 1999 Mar 12;274(11):7043-51. doi: 10.1074/jbc.274.11.7043.
Snake venom and mammalian secreted phospholipases A2 (sPLA2s) have been associated with toxic (neurotoxicity, myotoxicity, etc.), pathological (inflammation, cancer, etc.), and physiological (proliferation, contraction, secretion, etc.) processes. Specific membrane receptors (M and N types) for sPLA2s have been initially identified with snake venom sPLA2s as ligands, and the M-type 180-kDa receptor was cloned from different animal species. This paper addresses the problem of the endogenous ligands of the M-type receptor. Recombinant group IB and group IIA sPLA2s from human and mouse species have been prepared and analyzed for their binding properties to M-type receptors from different animal species. Both mouse group IB and group IIA sPLA2s are high affinity ligands (in the 1-10 nM range) for the mouse M-type receptor. These two sPLA2s are expressed in the mouse tissues where the M-type receptor is also expressed, making it likely that both types of sPLA2s are physiological ligands of the mouse M-type receptor. This conclusion does not hold for human group IB and IIA sPLA2s and the cloned human M-type receptor. The two mouse sPLA2s have relatively high affinities for the mouse M-type receptor, but they can have much lower affinities for receptors from other animal species, indicating that species specificity exists for sPLA2 binding to M-type receptors. Caution should thus be exerted in avoiding mixing sPLA2s, cells, or tissues from different animal species in studies of the biological roles of mammalian sPLA2s associated with an action through their membrane receptors.
蛇毒和哺乳动物分泌型磷脂酶A2（sPLA2s）与毒性（神经毒性、肌毒性等）、病理（炎症、癌症等）和生理（增殖、收缩、分泌等）过程有关。sPLA2s的特异性膜受体（M型和N型）最初是以蛇毒sPLA2s作为配体来鉴定的，并且从不同动物物种中克隆出了M型180-kDa受体。本文探讨了M型受体的内源性配体问题。已经制备了来自人和小鼠物种的重组IB组和IIA组sPLA2s，并分析了它们与不同动物物种M型受体的结合特性。小鼠IB组和IIA组sPLA2s都是小鼠M型受体的高亲和力配体（在1-10 nM范围内）。这两种sPLA2s在小鼠M型受体也表达的小鼠组织中表达，这使得这两种类型的sPLA2s都有可能是小鼠M型受体的生理配体。这一结论不适用于人IB组和IIA组sPLA2s以及克隆的人M型受体。这两种小鼠sPLA2s对小鼠M型受体具有相对较高的亲和力，但它们对其他动物物种的受体亲和力可能低得多，这表明sPLA2与M型受体结合存在物种特异性。因此，在研究与通过其膜受体发挥作用相关的哺乳动物sPLA2s的生物学作用时，应谨慎避免混合来自不同动物物种的sPLA2s、细胞或组织。
