Ouabain-induced endocytosis and signal transduction of the Na/K-ATPase.
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.
Liu
Jiang
J
Department of Medicine, Medical College of Ohio, 3120 Glendale Avenue, Toledo, Ohio 43614-5809, USA. jiliu@mco.edu
D000818:Animals; D002298:Cardenolides / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D007668:Kidney / Q000378:metabolism; D018374:LLC-PK1 Cells; D010042:Ouabain / Q000494:pharmacology*; D012503:Saponins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D002298:Cardenolides; D012503:Saponins; C034504:digoxin-like factors; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase