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Title: Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-activated protein kinase (AMPK).
Austin Authors: Fraser, Scott A;Gimenez, Ignacio;Cook, Natasha ;Jennings, Ian;Katerelos, Marina ;Katsis, Frosa;Levidiotis, Vicki;Kemp, Bruce E;Power, David Anthony
The Burnet Research Institute, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia
Issue Date: 1-Jul-2007
Publication information: The Biochemical Journal; 405(1): 85-93
Abstract: The renal-specific NKCC2 (Na+-K+-2Cl- co-transporter 2) is regulated by changes in phosphorylation state, however, the phosphorylation sites and kinases responsible have not been fully elucidated. In the present study, we demonstrate that the metabolic sensing kinase AMPK (AMP-activated protein kinase) phosphorylates NKCC2 on Ser126 in vitro. Co-precipitation experiments indicated that there is a physical association between AMPK and the N-terminal cytoplasmic domain of NKCC2. Activation of AMPK in the MMDD1 (mouse macula densa-derived 1) cell line resulted in an increase in Ser126 phosphorylation in situ, suggesting that AMPK may phosphorylate NKCC2 in vivo. The functional significance of Ser126 phosphorylation was examined by mutating the serine residue to an alanine residue resulting in a marked reduction in co-transporter activity when exogenously expressed in Xenopus laevis oocytes under isotonic conditions. Under hypertonic conditions no significant change of activity was observed. Therefore the present study identifies a novel phosphorylation site that maintains NKCC2-mediated transport under isotonic or basal conditions. Moreover, the metabolic-sensing kinase, AMPK, is able to phosphorylate this site, potentially linking the cellular energy state with changes in co-transporter activity.
Gov't Doc #: 17341212
DOI: 10.1042/BJ20061850
Journal: The Biochemical journal
Type: Journal Article
Subjects: AMP-Activated Protein Kinases
Amino Acid Sequence
Antibodies, Phospho-Specific.metabolism
Cell Line
Enzyme Activation
Molecular Sequence Data
Multienzyme Complexes.genetics.metabolism
Protein-Serine-Threonine Kinases.genetics.metabolism
Recombinant Fusion Proteins.genetics.metabolism
Reproducibility of Results
Sequence Alignment
Sodium-Potassium-Chloride Symporters.genetics.metabolism
Solute Carrier Family 12, Member 1
Xenopus laevis
Appears in Collections:Journal articles

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