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Activation of AMPK reduces the co-transporter activity of NKCC1
Fraser, Scott A. Davies, Matthew Katerelos, Marina Gleich, Kurt Choy, Suet-Wan Steel, Rohan Galic, Sandra Mount, Peter F. Kemp, Bruce E. Power, David A.
Fraser, Scott A.
Davies, Matthew
Katerelos, Marina
Gleich, Kurt
Choy, Suet-Wan
Steel, Rohan
Galic, Sandra
Mount, Peter F.
Kemp, Bruce E.
Power, David A.
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 NKCC1T212/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.
Keywords
cell biology, epithelial cell, Na-coupled transport
Date
1999
Type
Journal article
Journal
Molecular Membrane Biology
Book
Volume
31
Issue
2-3
Page Range
95-102
Article Number
ACU Department
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled