Activation of AMPK reduces the co-transporter activity of NKCC1
Journal article
Fraser, Scott A., Davies, Matthew R. P., Katerelos, Marina, Gleich, Kurt, Choy, Suet-Wan, Steel, Rohan, Galic, Sandra, Mount, Peter F., Kemp, Bruce Ernest and Power, David A.. (2014). Activation of AMPK reduces the co-transporter activity of NKCC1. Molecular Membrane Biology. 31(2-3), pp. 95 - 102. https://doi.org/10.3109/09687688.2014.902128
Authors | Fraser, Scott A., Davies, Matthew R. P., Katerelos, Marina, Gleich, Kurt, Choy, Suet-Wan, Steel, Rohan, Galic, Sandra, Mount, Peter F., Kemp, Bruce Ernest and Power, David A. |
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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 |
Year | 2014 |
Journal | Molecular Membrane Biology |
Journal citation | 31 (2-3), pp. 95 - 102 |
Publisher | Taylor & Francis |
ISSN | 0968-7688 |
Digital Object Identifier (DOI) | https://doi.org/10.3109/09687688.2014.902128 |
Scopus EID | 2-s2.0-84899463542 |
Page range | 95 - 102 |
Publisher's version | File Access Level Controlled |
Place of publication | United Kingdom |
https://acuresearchbank.acu.edu.au/item/889q6/activation-of-ampk-reduces-the-co-transporter-activity-of-nkcc1
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