Adrenergic, dopaminergic and muscarinic receptor stimulation leads to protein kinase a phosphorylation of na,k-atpase in cos-7 cells. Beguin, Pascal, Ahmed Beggah, Susanna Cotecchia, and K[umlaut]athi Geering. Institute of Pharmacology and Toxicology, University of Lausanne, rue du Bugnon 27, 1010 Lausanne, Switzerland
APStracts 2:0297C, 1995.
Na,K-ATPase is a potential target for phosphorylation by protein kinase A (PKA) and C (PKC). We have investigated whether the Na,K -ATPase [alpha] subunit becomes phosphorylated at its PKA or PKC phosphorylation sites upon stimulation of G protein - coupled receptors primarily linked either to the PKA or the PKC pathway. COS -7 cells, transiently or stably expressing Bufo Na,K-ATPase wild type (wt) [alpha] or mutant [alpha] subunits affected in its PKA or PKC phosphorylation site, were transfected with recombinant DNA encoding [beta]2- or [alpha]1- adrenergic (AR), dopaminergic (D1A-R) or muscarinic cholinergic (M1-AchR) receptor subspecies. Agonist stimulation of [beta]2-AR or D1A-R led to phosphorylation of the wt [alpha] as well as the PKC mutant but not of the PKA mutant indicating that these receptors can phosphorylate the Na,K-ATPase via PKA activation. Surprisingly, stimulation of the [alpha]1B-AR, a1C-AR and M1-AchR also increased the phosphorylation of the wt [alpha] and its PKC mutant, but not of its PKA mutant. Thus, the phosphorylation induced by these primarily phospholipase C-linked receptors, seems mainly mediated by PKA activation. These data indicate that the Na,K -ATPase [alpha] subunit can act as an ultimate target for PKA phosphorylation in a cascade starting with agonist - receptor interaction and leading finally to a phosphorylation - mediated regulation of the enzyme. 

Received 8 June 1995; accepted in final form 28 July 1995.
APS Manuscript Number C320-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.