| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA
* To whom correspondence should be addressed. E-mail: igimenez{at}unizar.es.
Short-term regulation of members of the Na-K-Cl cotransporter family takes place by phosphorylation/dephosphorylation events. Three N-terminal threonines have been previously identified as phosphoacceptors involved in activation of the ubiquitous/secretory Na-K-Cl cotransporter, NKCC1. In this report, 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 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 N-terminal cytosolic domain of NKCC2 upstream of the threonine regulatory domain, including the recently identified PASK 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.
This article has been cited by other articles:
|
|
 |
|
  G. Gamba The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs Am J Physiol Renal Physiol, October 1, 2009; 297(4): F838 - F848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Cook, S. A. Fraser, M. Katerelos, F. Katsis, K. Gleich, P. F. Mount, G. R. Steinberg, V. Levidiotis, B. E. Kemp, and D. A. Power Low salt concentrations activate AMP-activated protein kinase in mouse macula densa cells Am J Physiol Renal Physiol, April 1, 2009; 296(4): F801 - F809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Gonzales, T. Pisitkun, J. D. Hoffert, D. Tchapyjnikov, R. A. Star, R. Kleta, N. S. Wang, and M. A. Knepper Large-Scale Proteomics and Phosphoproteomics of Urinary Exosomes J. Am. Soc. Nephrol., February 1, 2009; 20(2): 363 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Hoffmann, I. H. Lambert, and S. F. Pedersen Physiology of Cell Volume Regulation in Vertebrates Physiol Rev, January 1, 2009; 89(1): 193 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Richardson and D. R. Alessi The regulation of salt transport and blood pressure by the WNK-SPAK/OSR1 signalling pathway J. Cell Sci., October 15, 2008; 121(20): 3293 - 3304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Welker, A. Bohlick, K. Mutig, M. Salanova, T. Kahl, H. Schluter, D. Blottner, J. Ponce-Coria, G. Gamba, and S. Bachmann Renal Na+-K+-Cl- cotransporter activity and vasopressin-induced trafficking are lipid raft-dependent Am J Physiol Renal Physiol, September 1, 2008; 295(3): F789 - F802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
