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) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiki, K. Articles by Gamble, J. R. Search for Related Content PubMed PubMed Citation Articles by Hiki, K. Articles by Gamble, J. R. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 15, 10661-10667, April 9, 1999

Cloning, Characterization, and Chromosomal Location of a Novel Human K⁺-Cl Cotransporter

Kazuaki Hiki, Richard J. D'Andrea, Jill Furze, Joanna Crawford, Erica Woollatt, Grant R. Sutherland, Mathew A. Vadas, and Jennifer R. Gamble

From the  Department of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science and University of Adelaide, Adelaide, South Australia 5000 and  Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia

Differential display polymerase chain reaction has been used to isolate genes regulated in vascular endothelial cells by the angiogenic factor vascular endothelial cell growth factor (VEGF). Analysis of one of the bands consistently up-regulated by VEGF led us to the identification of a cDNA from a human umbilical vein endothelial cell library that is 77% identical to the human K⁺-Cl cotransporter1 (KCC1). We have referred to the predicted protein as K⁺-Cl cotransporter 3 (KCC3). Hydrophobicity analysis of the KCC3 amino acid sequence showed an almost identical pattern to KCC1, suggesting 12 membrane-spanning segments, a large extracellular loop with potential N-glycosylation sites, and cytoplasmic N- and C-terminal regions. The KCC3 mRNA was highly expressed in brain, heart, skeletal muscle, and kidney, showing a distinct pattern and size from KCC1 and KCC2. The KCC3 mRNA level in endothelial cells increased on treatment with VEGF and decreased with the proinflammatory cytokine tumor necrosis factor , whereas KCC1 mRNA levels remained unchanged. Stable overexpression of KCC3 cDNA in HEK293 cells produced a glycoprotein of approximately 150 kDa, which was reduced to 120 kDa by glycosidase digestion. An increased initial uptake rate of ⁸⁶Rb was seen in clones with high KCC3 expression, which was dependent on extracellular Cl but not Na⁺ and was inhibitable by the loop diuretic agent furosemide. The KCC3 genomic localization was shown to be 15q13 by fluorescence in situ hybridization. Radiation hybrid analysis placed KCC3 within an area associated with juvenile myoclonic epilepsy. These results suggest KCC3 is a new member of the KCC family that is under distinct regulation from KCC1.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				H. Castrop and J. Schnermann Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance Am J Physiol Renal Physiol, October 1, 2008; 295(4): F859 - F866. [Abstract] [Full Text] [PDF]

				A. Salin-Cantegrel, M. Shekarabi, S. Holbert, P. Dion, D. Rochefort, J. Laganiere, S. Dacal, P. Hince, L. Karemera, C. Gaspar, et al. HMSN/ACC truncation mutations disrupt brain-type creatine kinase-dependant activation of K+/Cl- co-transporter 3 Hum. Mol. Genet., September 1, 2008; 17(17): 2703 - 2711. [Abstract] [Full Text] [PDF]

				Y.-M. Hsu, Y.-F. Chen, C.-Y. Chou, M.-J. Tang, J. H. Chen, R. J. Wilkins, J. C. Ellory, and M.-R. Shen KCl Cotransporter-3 Down-regulates E-Cadherin/{beta}-Catenin Complex to Promote Epithelial-Mesenchymal Transition Cancer Res., November 15, 2007; 67(22): 11064 - 11073. [Abstract] [Full Text] [PDF]

				A. Salin-Cantegrel, J. -B. Riviere, N. Dupre, F. M. Charron, M. Shekarabi, L. Karemera, C. Gaspar, J. Horst, M. Tekin, G. Deda, et al. Distal truncation of KCC3 in non French Canadian HMSN/ACC families Neurology, September 25, 2007; 69(13): 1350 - 1355. [Abstract] [Full Text] [PDF]

				C. F. Simard, M. J. Bergeron, R. Frenette-Cotton, G. A. Carpentier, M.-E. Pelchat, L. Caron, and P. Isenring Homooligomeric and Heterooligomeric Associations between K+-Cl- Cotransporter Isoforms and between K+-Cl- and Na+-K+-Cl- Cotransporters J. Biol. Chem., June 22, 2007; 282(25): 18083 - 18093. [Abstract] [Full Text] [PDF]

				M. J. Bergeron, E. Gagnon, L. Caron, and P. Isenring Identification of Key Functional Domains in the C Terminus of the K+-Cl- Cotransporters J. Biol. Chem., June 9, 2006; 281(23): 15959 - 15969. [Abstract] [Full Text] [PDF]

				K.-S. N. Chee, J. Kistler, and P. J. Donaldson Roles for KCC Transporters in the Maintenance of Lens Transparency Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 673 - 682. [Abstract] [Full Text] [PDF]

				A. Mercado, V. Broumand, K. Zandi-Nejad, A. H. Enck, and D. B. Mount A C-terminal Domain in KCC2 Confers Constitutive K+-Cl- Cotransport J. Biol. Chem., January 13, 2006; 281(2): 1016 - 1026. [Abstract] [Full Text] [PDF]

				A. Mercado, N. Vazquez, L. Song, R. Cortes, A. H. Enck, R. Welch, E. Delpire, G. Gamba, and D. B. Mount NH2-terminal heterogeneity in the KCC3 K+-Cl- cotransporter Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1246 - F1261. [Abstract] [Full Text] [PDF]

				G. Gamba Molecular Physiology and Pathophysiology of Electroneutral Cation-Chloride Cotransporters Physiol Rev, April 1, 2005; 85(2): 423 - 493. [Abstract] [Full Text] [PDF]

				J. A Fraser, C. E. J Rang, J. A Usher-Smith, and C. L.-H Huang Slow volume transients in amphibian skeletal muscle fibres studied in hypotonic solutions J. Physiol., April 1, 2005; 564(1): 51 - 63. [Abstract] [Full Text] [PDF]

				C. Rivera, J. Voipio, and K. Kaila Two developmental switches in GABAergic signalling: the K+-Cl- cotransporter KCC2 and carbonic anhydrase CAVII J. Physiol., January 1, 2005; 562(1): 27 - 36. [Abstract] [Full Text] [PDF]

				M.-R. Shen, A.-C. Lin, Y.-M. Hsu, T.-J. Chang, M.-J. Tang, S. L. Alper, J. C. Ellory, and C.-Y. Chou Insulin-like Growth Factor 1 Stimulates KCl Cotransport, Which Is Necessary for Invasion and Proliferation of Cervical Cancer and Ovarian Cancer Cells J. Biol. Chem., September 17, 2004; 279(38): 40017 - 40025. [Abstract] [Full Text] [PDF]

				G.-P. Zhou, C. Wong, R. Su, S. C. Crable, K. P. Anderson, and P. G. Gallagher Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element Blood, June 1, 2004; 103(11): 4302 - 4309. [Abstract] [Full Text] [PDF]

				H. Ochiai, K. Higa, and H. Fujise Molecular Identification of K-Cl Cotransporter in Dog Erythroid Progenitor Cells J. Biochem., March 1, 2004; 135(3): 365 - 374. [Abstract] [Full Text] [PDF]

				E. Gagnon, M. J. Bergeron, G. M. Brunet, N. D. Daigle, C. F. Simard, and P. Isenring Molecular Mechanisms of Cl- Transport by the Renal Na+-K+-Cl- Cotransporter: IDENTIFICATION OF AN INTRACELLULAR LOCUS THAT MAY FORM PART OF A HIGH AFFINITY Cl--BINDING SITE J. Biol. Chem., February 13, 2004; 279(7): 5648 - 5654. [Abstract] [Full Text] [PDF]

				P. G.J.F. Starremans, F. F.J. Kersten, L. P.W.J. van den Heuvel, N. V.A.M. Knoers, and R. J.M. Bindels Dimeric Architecture of the Human Bumetanide-Sensitive Na-K-Cl Co-transporter J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3039 - 3046. [Abstract] [Full Text] [PDF]

				M.-R. Shen, C.-Y. Chou, K.-F. Hsu, Y.-M. Hsu, W.-T. Chiu, M.-J. Tang, S. L. Alper, and J. C. Ellory KCl Cotransport Is an Important Modulator of Human Cervical Cancer Growth and Invasion J. Biol. Chem., October 10, 2003; 278(41): 39941 - 39950. [Abstract] [Full Text] [PDF]

				H. Velazquez and T. Silva Cloning and localization of KCC4 in rabbit kidney: expression in distal convoluted tubule Am J Physiol Renal Physiol, July 1, 2003; 285(1): F49 - F58. [Abstract] [Full Text] [PDF]

				M. J. Bergeron, E. Gagnon, B. Wallendorff, J.-Y. Lapointe, and P. Isenring Ammonium transport and pH regulation by K+-Cl- cotransporters Am J Physiol Renal Physiol, July 1, 2003; 285(1): F68 - F78. [Abstract] [Full Text] [PDF]

				J. C. de Jong, P. H. G. M. Willems, F. J. M. Mooren, L. P. W. J. van den Heuvel, N. V. A. M. Knoers, and R. J. M. Bindels The Structural Unit of the Thiazide-sensitive NaCl Cotransporter Is a Homodimer J. Biol. Chem., June 27, 2003; 278(27): 24302 - 24307. [Abstract] [Full Text] [PDF]

				R. S. Hoover, E. Poch, A. Monroy, N. Vazquez, T. Nishio, G. Gamba, and S. C. Hebert N-Glycosylation at Two Sites Critically Alters Thiazide Binding and Activity of the Rat Thiazide-sensitive Na+:Cl- Cotransporter J. Am. Soc. Nephrol., February 1, 2003; 14(2): 271 - 282. [Abstract] [Full Text] [PDF]

				K. Piechotta, J. Lu, and E. Delpire Cation Chloride Cotransporters Interact with the Stress-related Kinases Ste20-related Proline-Alanine-rich Kinase (SPAK) and Oxidative Stress Response 1 (OSR1) J. Biol. Chem., December 20, 2002; 277(52): 50812 - 50819. [Abstract] [Full Text] [PDF]

				H. Fujise, K. Higa, T. Kanemaru, M. Fukuda, N. C. Adragna, and P. K. Lauf GSH depletion, K-Cl cotransport, and regulatory volume decrease in high-K/high-GSH dog red blood cells Am J Physiol Cell Physiol, December 1, 2001; 281(6): C2003 - C2009. [Abstract] [Full Text] [PDF]

				M.-R. Shen, C.-Y. Chou, K.-F. Hsu, H.-S. Liu, P. B. Dunham, E. J. Holtzman, and J. C. Ellory The KCl cotransporter isoform KCC3 can play an important role in cell growth regulation PNAS, November 20, 2001; (2001) 251388798. [Abstract] [Full Text] [PDF]

				S. Casula, B. E. Shmukler, S. Wilhelm, A. K. Stuart-Tilley, W. Su, M. N. Chernova, C. Brugnara, and S. L. Alper A Dominant Negative Mutant of the KCC1 K-Cl Cotransporter. BOTH N- AND C-TERMINAL CYTOPLASMIC DOMAINS ARE REQUIRED FOR K-Cl COTRANSPORT ACTIVITY J. Biol. Chem., November 2, 2001; 276(45): 41870 - 41878. [Abstract] [Full Text] [PDF]

				G. Gamba Alternative splicing and diversity of renal transporters Am J Physiol Renal Physiol, November 1, 2001; 281(5): F781 - F794. [Abstract] [Full Text] [PDF]

				M. L. Jennings and M. F. Adame Direct estimate of 1:1 stoichiometry of K+-Cl{-} cotransport in rabbit erythrocytes Am J Physiol Cell Physiol, September 1, 2001; 281(3): C825 - C832. [Abstract] [Full Text] [PDF]

				A. Mercado, P. de los Heros, N. Vazquez, P. Meade, D. B. Mount, and G. Gamba Functional and molecular characterization of the K-Cl cotransporter of Xenopus laevis oocytes Am J Physiol Cell Physiol, August 1, 2001; 281(2): C670 - C680. [Abstract] [Full Text] [PDF]

				M. C. Muzyamba, P. F. Speake, and J. S. Gibson Oxidants and regulation of K+-Cl- cotransport in equine red blood cells Am J Physiol Cell Physiol, October 1, 2000; 279(4): C981 - C989. [Abstract] [Full Text] [PDF]

				K. Strange, T. D. Singer, R. Morrison, and E. Delpire Dependence of KCC2 K-Cl cotransporter activity on a conserved carboxy terminus tyrosine residue Am J Physiol Cell Physiol, September 1, 2000; 279(3): C860 - C867. [Abstract] [Full Text] [PDF]

				T. Q. Vu, J. A. Payne, and D. R. Copenhagen Localization and Developmental Expression Patterns of the Neuronal K-Cl Cotransporter (KCC2) in the Rat Retina J. Neurosci., February 15, 2000; 20(4): 1414 - 1423. [Abstract] [Full Text] [PDF]

				J. Gibson, A. Cossins, and J. Ellory Oxygen-sensitive membrane transporters in vertebrate red cells J. Exp. Biol., January 5, 2000; 203(9): 1395 - 1407. [Abstract] [PDF]

				J. E. Race, F. N. Makhlouf, P. J. Logue, F. H. Wilson, P. B. Dunham, and E. J. Holtzman Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter Am J Physiol Cell Physiol, December 1, 1999; 277(6): C1210 - C1219. [Abstract] [Full Text] [PDF]

				W. Su, B. E. Shmukler, M. N. Chernova, A. K. Stuart-Tilley, L. de Franceschi, C. Brugnara, and S. L. Alper Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation Am J Physiol Cell Physiol, November 1, 1999; 277(5): C899 - C912. [Abstract] [Full Text] [PDF]

				L. Caron, F. Rousseau, E. Gagnon, and P. Isenring Cloning and Functional Characterization of a Cation-Cl- Cotransporter-interacting Protein J. Biol. Chem., October 6, 2000; 275(41): 32027 - 32036. [Abstract] [Full Text] [PDF]

				A. Mercado, L. Song, N. Vazquez, D. B. Mount, and G. Gamba Functional Comparison of the K+-Cl- Cotransporters KCC1 and KCC4 J. Biol. Chem., September 22, 2000; 275(39): 30326 - 30334. [Abstract] [Full Text] [PDF]

				P. Sangan, S. R. Brill, S. Sangan, B. Forbush III, and H. J. Binder Basolateral K-Cl Cotransporter Regulates Colonic Potassium Absorption in Potassium Depletion J. Biol. Chem., September 29, 2000; 275(40): 30813 - 30816. [Abstract] [Full Text] [PDF]

				M. Di Fulvio, T. M. Lincoln, P. K. Lauf, and N. C. Adragna Protein Kinase G Regulates Potassium Chloride Cotransporter-3 Expression in Primary Cultures of Rat Vascular Smooth Muscle Cells J. Biol. Chem., June 8, 2001; 276(24): 21046 - 21052. [Abstract] [Full Text] [PDF]

				M. Di Fulvio, P. K. Lauf, and N. C. Adragna Nitric Oxide Signaling Pathway Regulates Potassium Chloride Cotransporter-1 mRNA Expression in Vascular Smooth Muscle Cells J. Biol. Chem., November 21, 2001; 276(48): 44534 - 44540. [Abstract] [Full Text] [PDF]

				M.-R. Shen, C.-Y. Chou, K.-F. Hsu, H.-S. Liu, P. B. Dunham, E. J. Holtzman, and J. C. Ellory The KCl cotransporter isoform KCC3 can play an important role in cell growth regulation PNAS, December 4, 2001; 98(25): 14714 - 14719. [Abstract] [Full Text] [PDF]