HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/F1341    most recent 00214.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Giménez, I. Articles by Forbush, B. Search for Related Content PubMed PubMed Citation Articles by Giménez, I. Articles by Forbush, B.

Regulatory phosphorylation sites in the NH₂ terminus of the renal Na-K-Cl cotransporter (NKCC2)

Department of Pharmacology and Physiology, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain; and Yale University School of Medicine, Department of Cellular and Molecular Physiology, New Haven, Connecticut

Short-term regulation of members of the Na-K-Cl cotransporter family takes place by phosphorylation/dephosphorylation events. Three NH₂-terminal threonines have been previously identified as phosphoacceptors involved in activation of the ubiquitous/secretory Na-K-Cl cotransporter (NKCC1). In this study, we demonstrate that the corresponding threonines are also involved in the regulation of the renal Na-K-Cl cotransporter (NKCC2). The transport activity of NKCC2, exogenously expressed in Xenopus laevis oocytes, is shown to be stimulated by hypertonicity. Mutagenic analysis demonstrated that threonines T99, T104, and T117 comprise a regulatory domain responsible for the activation of NKCC2 in hypertonic solutions: although none of the threonines was found to be individually necessary or sufficient for regulation, the three residues together are required to obtain the full hypertonic response. Under isotonic and hypotonic conditions, NKCC2 retains 50% of its activity in the absence of phosphorylation of the threonine-regulatory domain. Selective deletions of peptide segments revealed only a minor role for the NH₂-terminal cytosolic domain of NKCC2 upstream of the threonine regulatory domain, including the recently identified proline alanine-rich Ste-20-related kinase-binding motif. A chimeric NKCC containing the first 104 amino acids of NKCC1 on the NKCC2 backbone behaved essentially the same as NKCC2, further arguing against a major role for this upstream region in NKCC2 regulation.

renal sodium-potassium-chloride cotransporter

This article has been cited by other articles:

				H. Dimke, A. Flyvbjerg, S. Bourgeois, K. Thomsen, J. Frokiaer, P. Houillier, S. Nielsen, and S. Frische Acute growth hormone administration induces antidiuretic and antinatriuretic effects and increases phosphorylation of NKCC2 Am J Physiol Renal Physiol, February 1, 2007; 292(2): F723 - F735. [Abstract] [Full Text] [PDF]

				K. T. Kahle, J. Rinehart, A. Ring, I. Gimenez, G. Gamba, S. C. Hebert, and R. P. Lifton WNK Protein Kinases Modulate Cellular Cl- Flux by Altering the Phosphorylation State of the Na-K-Cl and K-Cl Cotransporters. Physiology, October 1, 2006; 21: 326 - 335. [Abstract] [Full Text] [PDF]

				C. Li, W. Wang, S. N. Summer, M. A. Cadnapaphornchai, S. Falk, F. Umenishi, and R. W. Schrier Hyperosmolality In Vivo Upregulates Aquaporin 2 Water Channel and Na-K-2Cl Co-Transporter in Brattleboro Rats J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1657 - 1664. [Abstract] [Full Text] [PDF]

				D. B. Mount Membrane trafficking and the regulation of NKCC2 Am J Physiol Renal Physiol, March 1, 2006; 290(3): F606 - F607. [Full Text] [PDF]