Department of Anesthesiology

You are here

Identification of the phosphorylation site for cAMP-dependent protein kinase on Na+,K(+)-ATPase and effects of site-directed mutagenesis.

TitleIdentification of the phosphorylation site for cAMP-dependent protein kinase on Na+,K(+)-ATPase and effects of site-directed mutagenesis.
Publication TypeJournal Article
Year of Publication1994
AuthorsFisone G, Cheng SX, Nairn AC, Czernik AJ, Hemmings HC, Höög JO, Bertorello AM, Kaiser R, Bergman T, Jörnvall H
JournalJ Biol Chem
Volume269
Issue12
Pagination9368-73
Date Published1994 Mar 25
ISSN0021-9258
Keywords1-Methyl-3-isobutylxanthine, Amino Acid Sequence, Animals, Base Sequence, Cyclic AMP-Dependent Protein Kinases, DNA Primers, Forskolin, Kinetics, Molecular Sequence Data, Mutagenesis, Site-Directed, Peptide Mapping, Peptides, Phosphoserine, Rats, Recombinant Proteins, Sodium-Potassium-Exchanging ATPase, Structure-Activity Relationship
Abstract

Phosphorylation of purified Na+,K(+)-ATPase by cAMP-dependent protein kinase (protein kinase A) decreases the activity of this enzyme. We have now shown, using several experimental approaches, that a highly conserved seryl residue on the catalytic (alpha) subunit of Na+,K(+)-ATPase, corresponding to Ser943 of the rat alpha 1 isoform, is the phosphorylation site for protein kinase A. cDNAs corresponding to wild-type Na+,K(+)-ATPase and Na+,K(+)-ATPase in which Ser943 was mutated to Ala were transfected into COS cells. Treatment of the transfected cells with forskolin plus 3-isobutyl-1-methylxanthine resulted in a decrease in the activity of the wild-type enzyme but not in that of the mutated enzyme. The results suggest that, in intact cells, the activity of the Na+,K(+)-ATPase is regulated in part by signal transduction pathways that use protein kinase A-dependent phosphorylation of the Na+,K(+)-ATPase alpha subunit.

Alternate JournalJ. Biol. Chem.
PubMed ID7510709
Grant ListMH-40899 / MH / NIMH NIH HHS / United States