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哇巴因诱导的钠钾ATP酶的内吞作用和信号转导

Ouabain-induced endocytosis and signal transduction of the Na/K-ATPase.

作者信息

Liu Jiang

机构信息

Department of Medicine, Medical College of Ohio, 3120 Glendale Avenue, Toledo, Ohio 43614-5809, USA.

出版信息

Front Biosci. 2005 Sep 1;10:2056-63. doi: 10.2741/1681.

DOI:10.2741/1681
PMID:15970478
Abstract

Na/K-ATPase can function as a signal transducer as well as an energy transducing ion pump. Cardiac glycosides (including ouabain and marinobufagin, MBG) are a new class of steroid hormones. Ouabain-activated signaling pathways lead to the induction of some early response proto-oncogenes, activation of transcription factors, and cardiac hypertrophy. Low concentration of ouabain also induced endocytosis of the Na/K-ATPase and compartmentalization of some signaling molecules (e.g. c-Src, EGFR, and p42/44 MAPKs) into clathrin-coated pits, early and late endosomes. Ouabain-induced endocytosis of the Na/K-ATPase depends on the activation of Src kinase, clathrin-coated pits formation, and caveolin-1 (the major component of caveolae). Moreover, low concentration ouabain significantly reduced transcellular Na+ transport. The data also show a stronge interplay of ouabain-induced endocytosis of the Na/K-ATPase and signaling transduction.

摘要

钠钾ATP酶既可以作为信号转导器,也可以作为能量转换离子泵发挥作用。强心苷(包括哇巴因和蟾蜍灵,MBG)是一类新型甾体激素。哇巴因激活的信号通路可导致一些早期反应原癌基因的诱导、转录因子的激活以及心肌肥大。低浓度的哇巴因还可诱导钠钾ATP酶的内吞作用,并使一些信号分子(如c-Src、表皮生长因子受体和p42/44丝裂原活化蛋白激酶)分隔到网格蛋白包被小窝、早期和晚期内体中。哇巴因诱导的钠钾ATP酶内吞作用依赖于Src激酶的激活、网格蛋白包被小窝的形成以及小窝蛋白-1(小窝的主要成分)。此外,低浓度的哇巴因显著降低跨细胞的钠离子转运。这些数据还表明哇巴因诱导的钠钾ATP酶内吞作用与信号转导之间存在强烈的相互作用。

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