beta-Agonists regulate Na,K-ATPase via novel MAPK/ERK and rapamycin-sensitive pathways

We studied whether the beta -adrenergic agonist, isoproterenol (ISO), regul ates Na,K-ATPase in alveolar epithelial cells (AEC) via a mitogen-activated protein kinase (MAPK)/ extracellular signaling related kinase (ERK) depend ent pathway. ISO increased ERK activity in AEC by 10 min via a beta -adrene rgic receptor, protein kinase A (PKA)-dependent mechanism. Activation of th e MAPK pathway by ISO, resulted in increased Na,K-ATPase beta 1and alpha1 s ubunit protein abundance in whole cell lysates, which resulted in functiona l Na,K-ATPases at the basolateral membranes. ISO did not change the alpha1 or beta1 mRNA steady state levels, but rapamycin, the inhibitor of the mamm alian target of rapamycin, also blocked the ISO-mediated increase in Na,K-A TPase total protein abundance, suggesting a posttranscriptional regulation. We conclude that ISO, regulates the Na,K-ATPase in AEC via PKA, ERK and ra pamycin-sensitive mechanisms. (C) 2000 Federation of European Biochemical S ocieties. Published by Elsevier Science B.V. All rights reserved.