| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 22, 16795-16801, June 2, 2000
From the Departments of Pharmacology and ¶ Biochemistry, The
University of Texas Southwestern Medical Center,
Dallas, Texas 75390-9041
We have cloned and characterized a novel
mammalian serine/threonine protein kinase WNK1 (with
no lysine (K)) from a rat brain cDNA
library. WNK1 has 2126 amino acids and can be detected as a protein of
~230 kDa in various cell lines and rat tissues. WNK1 contains a small
N-terminal domain followed by the kinase domain and a long C-terminal
tail. The WNK1 kinase domain has the greatest similarity to the MEKK
protein kinase family. However, overexpression of WNK1 in HEK293 cells
exerts no detectable effect on the activity of known, co-transfected
mitogen-activated protein kinases, suggesting that it belongs to a
distinct pathway. WNK1 phosphorylates the exogenous substrate myelin
basic protein as well as itself mostly on serine residues, confirming
that it is a serine/threonine protein kinase. The demonstration of
activity was striking because WNK1, and its homologs in other organisms
lack the invariant catalytic lysine in subdomain II of protein kinases
that is crucial for binding to ATP. A model of WNK1 using the structure
of cAMP-dependent protein kinase suggests that lysine 233 in kinase subdomain I may provide this function. Mutation of this
lysine residue to methionine eliminates WNK1 activity, consistent with
the conclusion that it is required for catalysis. This distinct
organization of catalytic residues indicates that WNK1 belongs to a
novel family of serine/threonine protein kinases.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF227741.
WNK1, a Novel Mammalian Serine/Threonine Protein Kinase Lacking
the Catalytic Lysine in Subdomain II*
,
*
This work was supported by National Institutes of Health
Grants DK34128 and GM53032.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Dept. of Biological Research-Oncology,
Schering-Plough Research Inst., Kenilworth, NJ 07033.
§
Supported by a predoctoral fellowship from the Howard Hughes
Medical Institute. Present address: Dept. of Cell Biology, Harvard Medical School, Boston, MA 02115.
To whom correspondence should be addressed: UT Southwestern
Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9041. Tel.:
214-648-3627; Fax: 214-648-3811; E-mail: melanie.cobb@email. swmed.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Zhang, T. Na, and J.-B. Peng WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1472 - F1484. [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. San-Cristobal, J. Ponce-Coria, N. Vazquez, N. A. Bobadilla, and G. Gamba WNK3 and WNK4 amino-terminal domain defines their effect on the renal Na+-Cl- cotransporter Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1199 - F1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-R. Wang, Z. Liu, and C.-L. Huang Domains of WNK1 kinase in the regulation of ROMK1 Am J Physiol Renal Physiol, August 1, 2008; 295(2): F438 - F445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ponce-Coria, P. San-Cristobal, K. T. Kahle, N. Vazquez, D. Pacheco-Alvarez, P. de los Heros, P. Juarez, E. Munoz, G. Michel, N. A. Bobadilla, et al. Regulation of NKCC2 by a chloride-sensing mechanism involving the WNK3 and SPAK kinases PNAS, June 17, 2008; 105(24): 8458 - 8463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. McCormick, C.-L. Yang, and D. H. Ellison WNK Kinases and Renal Sodium Transport in Health and Disease: An Integrated View Hypertension, March 1, 2008; 51(3): 588 - 596. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Oh, C. J. Heise, J. M. English, M. H. Cobb, and D. C. Thurmond WNK1 Is a Novel Regulator of Munc18c-Syntaxin 4 Complex Formation in Soluble NSF Attachment Protein Receptor (SNARE)-mediated Vesicle Exocytosis J. Biol. Chem., November 9, 2007; 282(45): 32613 - 32622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Dorwart, N. Shcheynikov, Y. Wang, S. Stippec, and S. Muallem SLC26A9 is a Cl channel regulated by the WNK kinases J. Physiol., October 1, 2007; 584(1): 333 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-B. Peng and D. G. Warnock WNK4-mediated regulation of renal ion transport proteins Am J Physiol Renal Physiol, October 1, 2007; 293(4): F961 - F973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. Choe and K. Strange Evolutionarily conserved WNK and Ste20 kinases are essential for acute volume recovery and survival after hypertonic shrinkage in Caenorhabditis elegans Am J Physiol Cell Physiol, September 1, 2007; 293(3): C915 - C927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hong, K. S. Moorefield, P. Jun, K. D. Aldape, S. Kharbanda, H. S. Phillips, and J. F. Costello Epigenome scans and cancer genome sequencing converge on WNK2, a kinase-independent suppressor of cell growth PNAS, June 26, 2007; 104(26): 10974 - 10979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-H. Lee, W. Chen, S. Stippec, and M. H. Cobb Biological Cross-talk between WNK1 and the Transforming Growth Factor beta-Smad Signaling Pathway J. Biol. Chem., June 22, 2007; 282(25): 17985 - 17996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Sonalker and E. K. Jackson Norepinephrine, via {beta}-Adrenoceptors, Regulates Bumetanide-Sensitive Cotransporter Type 1 Expression in Thick Ascending Limb Cells Hypertension, June 1, 2007; 49(6): 1351 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Garzon-Muvdi, D. Pacheco-Alvarez, K. B. E. Gagnon, N. Vazquez, J. Ponce-Coria, E. Moreno, E. Delpire, and G. Gamba WNK4 kinase is a negative regulator of K+-Cl- cotransporters Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1197 - F1207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-W. Tam, N. F. Wilson, and P. A. Lefebvre A CDK-related kinase regulates the length and assembly of flagella in Chlamydomonas J. Cell Biol., March 12, 2007; 176(6): 819 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Jiang, W. B. Ferguson, and J.-B. Peng WNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria of familial hyperkalemic hypertension caused by gene mutation of WNK4 Am J Physiol Renal Physiol, February 1, 2007; 292(2): F545 - F554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zagorska, E. Pozo-Guisado, J. Boudeau, A. C. Vitari, F. H. Rafiqi, J. Thastrup, M. Deak, D. G. Campbell, N. A. Morrice, A. R. Prescott, et al. Regulation of activity and localization of the WNK1 protein kinase by hyperosmotic stress J. Cell Biol., January 1, 2007; 176(1): 89 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Golbang, G. Cope, A. Hamad, M. Murthy, C.-H. Liu, A. W. Cuthbert, and K. M. O'Shaughnessy Regulation of the expression of the Na/Cl cotransporter by WNK4 and WNK1: evidence that accelerated dynamin-dependent endocytosis is not involved Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1369 - F1376. [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]
|
|
|
|
|
|
D. Pacheco-Alvarez, P. S. Cristobal, P. Meade, E. Moreno, N. Vazquez, E. Munoz, A. Diaz, M. E. Juarez, I. Gimenez, and G. Gamba The Na+:Cl- Cotransporter Is Activated and Phosphorylated at the Amino-terminal Domain upon Intracellular Chloride Depletion J. Biol. Chem., September 29, 2006; 281(39): 28755 - 28763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O'Reilly, E. Marshall, T. MacGillivray, M. Mittal, W. Xue, C. J. Kenyon, and R. W. Brown Dietary Electrolyte-Driven Responses in the Renal WNK Kinase Pathway In Vivo J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2402 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Anselmo, S. Earnest, W. Chen, Y.-C. Juang, S. C. Kim, Y. Zhao, and M. H. Cobb WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells PNAS, July 18, 2006; 103(29): 10883 - 10888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Delaloy, J. Hadchouel, M. Imbert-Teboul, M. Clemessy, A.-M. Houot, and X. Jeunemaitre Cardiovascular Expression of the Mouse WNK1 Gene during Development and Adulthood Revealed by a BAC Reporter Assay Am. J. Pathol., July 1, 2006; 169(1): 105 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Cope, M. Murthy, A. P. Golbang, A. Hamad, C.-H. Liu, A. W. Cuthbert, and K. M. O'Shaughnessy WNK1 Affects Surface Expression of the ROMK Potassium Channel Independent of WNK4 J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1867 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Fu, A. Subramanya, D. Rozansky, and D. M. Cohen WNK kinases influence TRPV4 channel function and localization Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1305 - F1314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Wade, L. Fang, J. Liu, D. Li, C.-L. Yang, A. R. Subramanya, D. Maouyo, A. Mason, D. H. Ellison, and P. A. Welling WNK1 kinase isoform switch regulates renal potassium excretion PNAS, May 30, 2006; 103(22): 8558 - 8563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. L. Yu WNK signaling in the distal tubule: an inhibitory cascade regulating salt transport Am J Physiol Renal Physiol, March 1, 2006; 290(3): F617 - F618. [Full Text] [PDF]
|
|
|
|
|
|
Q. Leng, K. T. Kahle, J. Rinehart, G. G. MacGregor, F. H. Wilson, C. M. Canessa, R. P. Lifton, and S. C. Hebert WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1) J. Physiol., March 1, 2006; 571(2): 275 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Subramanya, C.-L. Yang, X. Zhu, and D. H. Ellison Dominant-negative regulation of WNK1 by its kidney-specific kinase-defective isoform Am J Physiol Renal Physiol, March 1, 2006; 290(3): F619 - F624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lazrak, Z. Liu, and C.-L. Huang Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms PNAS, January 31, 2006; 103(5): 1615 - 1620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hadchouel, C. Delaloy, S. Faure, J.-M. Achard, and X. Jeunemaitre Familial Hyperkalemic Hypertension J. Am. Soc. Nephrol., January 1, 2006; 17(1): 208 - 217. [Full Text] [PDF]
|
|
|
|
|
|
K. B. E. Gagnon, R. England, and E. Delpire Volume sensitivity of cation-Cl- cotransporters is modulated by the interaction of two kinases: Ste20-related proline-alanine-rich kinase and WNK4 Am J Physiol Cell Physiol, January 1, 2006; 290(1): C134 - C142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Moriguchi, S. Urushiyama, N. Hisamoto, S.-i. Iemura, S. Uchida, T. Natsume, K. Matsumoto, and H. Shibuya WNK1 Regulates Phosphorylation of Cation-Chloride-coupled Cotransporters via the STE20-related Kinases, SPAK and OSR1 J. Biol. Chem., December 30, 2005; 280(52): 42685 - 42693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang and J. A. Staessen Association of Blood Pressure With Genetic Variation in WNK Kinases in a White European Population Circulation, November 29, 2005; 112(22): 3371 - 3372. [Full Text] [PDF]
|
|
|
|
|
|
J. Rinehart, K. T. Kahle, P. de los Heros, N. Vazquez, P. Meade, F. H. Wilson, S. C. Hebert, I. Gimenez, G. Gamba, and R. P. Lifton WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis PNAS, November 15, 2005; 102(46): 16777 - 16782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Kahle, J. Rinehart, P. de los Heros, A. Louvi, P. Meade, N. Vazquez, S. C. Hebert, G. Gamba, I. Gimenez, and R. P. Lifton WNK3 modulates transport of Cl- in and out of cells: Implications for control of cell volume and neuronal excitability PNAS, November 15, 2005; 102(46): 16783 - 16788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-e Xu, S. Stippec, A. Lazrak, C.-L. Huang, and M. H. Cobb WNK1 Activates SGK1 by a Phosphatidylinositol 3-Kinase-dependent and Non-catalytic Mechanism J. Biol. Chem., October 7, 2005; 280(40): 34218 - 34223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Y. Lenertz, B.-H. Lee, X. Min, B.-e Xu, K. Wedin, S. Earnest, E. J. Goldsmith, and M. H. Cobb Properties of WNK1 and Implications for Other Family Members J. Biol. Chem., July 22, 2005; 280(29): 26653 - 26658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-e Xu, S. Stippec, P.-Y. Chu, A. Lazrak, X.-J. Li, B.-H. Lee, J. M. English, B. Ortega, C.-L. Huang, and M. H. Cobb WNK1 activates SGK1 to regulate the epithelial sodium channel PNAS, July 19, 2005; 102(29): 10315 - 10320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Newhouse, C. Wallace, R. Dobson, C. Mein, J. Pembroke, M. Farrall, D. Clayton, M. Brown, N. Samani, A. Dominiczak, et al. Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British Genetics of Hypertension study Hum. Mol. Genet., July 1, 2005; 14(13): 1805 - 1814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Y. Jiang, Q. L. Zhou, J. Holik, S. Patel, J. Leszyk, K. Coleman, M. Chouinard, and M. P. Czech Identification of WNK1 as a Substrate of Akt/Protein Kinase B and a Negative Regulator of Insulin-stimulated Mitogenesis in 3T3-L1 Cells J. Biol. Chem., June 3, 2005; 280(22): 21622 - 21628. [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]
|
|
|
|
|
|
G. Gamba Role of WNK kinases in regulating tubular salt and potassium transport and in the development of hypertension Am J Physiol Renal Physiol, February 1, 2005; 288(2): F245 - F252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Naray-Fejes-Toth, P. M. Snyder, and G. Fejes-Toth The kidney-specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transport PNAS, December 14, 2004; 101(50): 17434 - 17439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Mayan, G. Munter, M. Shaharabany, M. Mouallem, R. Pauzner, E. J. Holtzman, and Z. Farfel Hypercalciuria in Familial Hyperkalemia and Hypertension Accompanies Hyperkalemia and Precedes Hypertension: Description of a Large Family with the Q565E WNK4 Mutation J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4025 - 4030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Xing, L. Campodonico, and R. Kolesnick The Kinase Activity of Kinase Suppressor of Ras1 (KSR1) Is Independent of Bound MEK J. Biol. Chem., June 18, 2004; 279(25): 26210 - 26214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamauchi, T. Rai, K. Kobayashi, E. Sohara, T. Suzuki, T. Itoh, S. Suda, A. Hayama, S. Sasaki, and S. Uchida Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins PNAS, March 30, 2004; 101(13): 4690 - 4694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chen, M. Yazicioglu, and M. H. Cobb Characterization of OSR1, a Member of the Mammalian Ste20p/Germinal Center Kinase Subfamily J. Biol. Chem., March 19, 2004; 279(12): 11129 - 11136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-e Xu, S. Stippec, L. Lenertz, B.-H. Lee, W. Zhang, Y.-K. Lee, and M. H. Cobb WNK1 Activates ERK5 by an MEKK2/3-dependent Mechanism J. Biol. Chem., February 27, 2004; 279(9): 7826 - 7831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Gallagher, S. Gutowski, P. C. Sternweis, and M. H. Cobb RhoA Binds to the Amino Terminus of MEKK1 and Regulates Its Kinase Activity J. Biol. Chem., January 16, 2004; 279(3): 1872 - 1877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Delaloy, J. Lu, A.-M. Houot, S. Disse-Nicodeme, J.-M. Gasc, P. Corvol, and X. Jeunemaitre Multiple Promoters in the WNK1 Gene: One Controls Expression of a Kidney-Specific Kinase-Defective Isoform Mol. Cell. Biol., December 15, 2003; 23(24): 9208 - 9221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Faure, C. Delaloy, V. Leprivey, J. Hadchouel, D. G. Warnock, X. Jeunemaitre, and J.-M. Achard WNK kinases, distal tubular ion handling and hypertension Nephrol. Dial. Transplant., December 1, 2003; 18(12): 2463 - 2467. [Full Text] [PDF]
|
|
|
|
|
|
B. P. Zambrowicz, A. Abuin, R. Ramirez-Solis, L. J. Richter, J. Piggott, H. BeltrandelRio, E. C. Buxton, J. Edwards, R. A. Finch, C. J. Friddle, et al. Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention PNAS, November 25, 2003; 100(24): 14109 - 14114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O'Reilly, E. Marshall, H. J.L. Speirs, and R. W. Brown WNK1, a Gene within a Novel Blood Pressure Control Pathway, Tissue-Specifically Generates Radically Different Isoforms with and without a Kinase Domain J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2447 - 2456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Giangrande, T. C. Hallstrom, C. Tunyaplin, K. Calame, and J. R. Nevins Identification of E-Box Factor TFE3 as a Functional Partner for the E2F3 Transcription Factor Mol. Cell. Biol., June 1, 2003; 23(11): 3707 - 3720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
