title: Na+/K+-ATPase-mediated signal transduction and Na+/K+-ATPase regulation.
abstract: A number of studies suggest that Na(+)/K(+)-ATPase in caveolae interacts with neighboring membrane proteins and organizes cytosolic cascades of signaling proteins to send messages to intracellular organelles in different tissues, mostly in cardiac myocytes. Low concentration of ouabain binding to Na(+)/K(+)-ATPase activates Src/epidermal growth factor receptor complex to initiate multiple signal pathways, which include PLC/IP3/CICR, PI3K, reactive oxygen species (ROS), PLC/DG/PKC/Raf/MEK/ERK1/2, and Ras/Raf/MEK/ERK1/2 pathways. In cardiac myocytes, the resulting downstream events include the induction of some early response proto-oncogenes, activation of transcription factors, activator protein-1, and nuclear factor-kappaB, the regulation of a number of cardiac growth-related genes, and the stimulation of protein synthesis and myocyte hypertrophy and apoptosis. Conversely, several factors acting through signal pathways, such as protein kinases, Ca(2+), ROS, etc., can modulate the activity of the Na(+)/K(+)-ATPase.
authors.affiliation: Department of Pharmacology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang City, Hebei Province, China.
authors.forename: Linan
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Huicai
authors.initials: H
authors.lastname: Guo
authors.forename: Yongli
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002147:Calmodulin / Q000378:metabolism; D021941:Caveolae / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D002147:Calmodulin; D017382:Reactive Oxygen Species; D000242:Cyclic AMP; D019061:src-Family Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP