Na+/K+-ATPase-mediated signal transduction and Na+/K+-ATPase regulation.
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.
Zhang
Linan
L
Department of Pharmacology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang City, Hebei Province, China.
Zhang
Zhe
Z
Guo
Huicai
H
Wang
Yongli
Y
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
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