GM2神经节苷脂激活剂对磷脂酶D激活的需求。
Requirement of GM2 ganglioside activator for phospholipase D activation.
作者信息
Nakamura S, Akisue T, Jinnai H, Hitomi T, Sarkar S, Miwa N, Okada T, Yoshida K, Kuroda S, Kikkawa U, Nishizuka Y
机构信息
Department of Biochemistry, Kobe University School of Medicine, Kobe 650-0017, Japan.
出版信息
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12249-53. doi: 10.1073/pnas.95.21.12249.
Sequence analysis of a heat-stable protein necessary for the activation of ADP ribosylation factor-dependent phospholipase D (PLD) reveals that this protein has a structure highly homologous to the previously known GM2 ganglioside activator whose deficiency results in the AB-variant of GM2 gangliosidosis. The heat-stable activator protein indeed has the capacity to enhance enzymatic conversion of GM2 to GM3 ganglioside that is catalyzed by beta-hexosaminidase A. Inversely, GM2 ganglioside activator purified separately from tissues as described earlier [Conzelmann, E. & Sandhoff, K. (1987) Methods Enzymol. 138, 792-815] stimulates ADP ribosylation factor-dependent PLD in a dose-dependent manner. At higher concentrations of ammonium sulfate, the PLD activator protein apparently substitutes for protein kinase C and phosphatidylinositol 4,5-bisphosphate, both of which are known as effective stimulators of the PLD reaction. The mechanism of action of the heat-stable PLD activator protein remains unknown.
对ADP核糖基化因子依赖性磷脂酶D（PLD）激活所必需的一种热稳定蛋白进行序列分析发现，该蛋白具有与先前已知的GM2神经节苷脂激活剂高度同源的结构，其缺乏会导致GM2神经节苷脂沉积症的AB变异型。这种热稳定激活蛋白确实具有增强由β-己糖胺酶A催化的GM2向GM3神经节苷脂酶促转化的能力。相反，如前所述[Conzelmann, E. & Sandhoff, K. (1987) Methods Enzymol. 138, 792 - 815]从组织中单独纯化的GM2神经节苷脂激活剂以剂量依赖方式刺激ADP核糖基化因子依赖性PLD。在较高浓度的硫酸铵下，PLD激活蛋白显然替代了蛋白激酶C和磷脂酰肌醇4,5-二磷酸，这两者均为已知的PLD反应有效刺激剂。热稳定PLD激活蛋白的作用机制仍然未知。
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