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Title: Activation of AMPK reduces the co-transporter activity of NKCC1.
Austin Authors: Fraser, Scott A;Davies, Matthew R P ;Katerelos, Marina ;Gleich, Kurt;Choy, Suet-Wan ;Steel, Rohan;Galic, Sandra;Mount, Peter F ;Kemp, Bruce E;Power, David A 
Affiliation: Institute for Breathing and Sleep
Issue Date: May-2014
Date: 2014-04
Publication information: Molecular Membrane Biology 2014;31(2-3): 95-102
Abstract: The co-transporter activity of Na(+)-K(+)-2Cl(-) 1 (NKCC1) is dependent on phosphorylation. In this study we show the energy-sensing kinase AMPK inhibits NKCC1 activity. Three separate AMPK activators (AICAR, Phenformin and A-769662) inhibited NKCC1 flux in a variety of nucleated cells. Treatment with A-769662 resulted in a reduction of NKCC1(T212/T217) phosphorylation, and this was reversed by treatment with the non-selective AMPK inhibitor Compound C. AMPK dependence was confirmed by treatment of AMPK null mouse embryonic fibroblasts, where A-769662 had no effect on NKCC1 mediated transport. AMPK was found to directly phosphorylate a recombinant human-NKCC1 N-terminal fragment (1-293) with the phosphorylated site identified as S77. Mutation of Serine 77 to Alanine partially prevented the inhibitory effect of A-769662 on NKCC1 activity. In conclusion, AMPK can act to reduce NKCC1-mediated transport. While the exact mechanism is still unclear there is evidence for both a direct effect on phosphorylation of S77 and reduced phosphorylation of T212/217.
DOI: 10.3109/09687688.2014.902128
Journal: Molecular Membrane Biology
PubMed URL: 24702155
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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