We are seeing patients in-person and through Video Visits. Learn more about how we’re keeping you safe and please review our updated visitor policy. Please also consider supporting Weill Cornell Medicine’s efforts to support our front-line workers.
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