期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 10, 期 -, 页码 2056-2063出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/1681
关键词
Na/K-ATPase; ouabain; endocytosis; Src kinase; NHE3; digitalis; signaling; calthrin; caveolin; review
资金
- NHLBI NIH HHS [HL57144, HL63238, HL67963] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL067963, P50HL057144, R01HL063238] Funding Source: NIH RePORTER
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 srtonge interplay of ouabain-induced endocytosis of the Na/K-ATPase and signaling transduction.
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