Beta-adrenergic agonists regulate Na-K-ATPase via p70S6k.
We have recently reported that the beta-adrenergic agonist isoproterenol regulates the alveolar epithelial cell Na-K-ATPase via MAPK/extracellular signal-regulated kinase and rapamycin-sensitive pathways. Here we report that isoproterenol phosphorylated the protein S6 kinase (p70S6k) in alveolar epithelial cells, which was inhibited by both rapamycin and the MEK1/2 inhibitor U-0126. In alveolar epithelial cells transfected with a p70S6k dominant negative construct, isoproterenol did not increase Na-K-ATPase total protein expression, whereas in cells transfected with a rapamycin-resistant mutant, the isoproterenol-mediated increase in Na-K-ATPase was not prevented by rapamycin. Accordingly, we provide here first evidence that isoproterenol regulates Na-K-ATPase via p70S6k in alveolar epithelial cells.
Pesce
Liuska
L
Pulmonary and Critical Care Medicine, Northwestern Univ., 303 E. Chicago Ave., Tarry Bldg. 14-707, Chicago, IL 60611, USA.
Comellas
Alejandro
A
Sznajder
Jacob I
JI
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D000318:Adrenergic beta-Agonists; D066246:ErbB Receptors; D007545:Isoproterenol; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus; D000254:Sodium-Potassium-Exchanging ATPase; D058570:TOR Serine-Threonine Kinases