Abstract
We have cloned and characterized a novel human serine/threonine protein kinase gene from chromosome 12p13.3 encoding 2382 amino acids. Remarkably, the catalytic domain sequence contains a cysteine in place of a lysine residue conserved in subdomain II of most kinases. The same amino acid alteration was recently described for rat WNK1 (with no K = lysine) in which another nearby lysine residue was shown to confer kinase activity to the protein. Rat WNK1 is 85% identical to a splice variant lacking exons 11 and 12 of the described human kinase which we have called human WNK1. The WNK1 catalytic domain has closest homology with human PAK2, MEKK3, and Raf-1. Three additional, partial human protein kinase sequences, WNK2, WNK3 and WNK4, are also reported here with catalytic domains that are 95% homologous to WNK1. These genes differ both in chromosomal location and tissue-specific expression. Moreover, we have identified in the database a total of 18 WNK-related genes, all exclusively from multi-cellular organisms, which share a WNK kinase sequence signature within subdomains I and II of the catalytic domain. We suggest that they constitute a novel subfamily of protein kinases that evolved together with cell adhesion and tissue-formation.
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References
Bossemeyer D, Engh RA, Kinzel V, Ponstingl H, Huber R . 1993 EMBO J. 12: 849–859
Bossemeyer D . 1994 Trends Biochem Sci. 19: 201–205
Chang L, Karin M . 2001 Nature 410: 37–40
Denhardt DT . 1996 Biochem J. 318: 729–747
Dhanasekaran N . 1998 Oncogene 17: 1329–1330
Dhanasekaran N, Reddy EP . 1998 Oncogene 17: 1447–1455
Garrington TP, Johnson GI . 1999 Curr. Biol. 11: 211–218
Hanks SK, Hunter T . 1995 FASEB J. 9: 576–596
Hunter T . 2000 Cell 100: 113–127
Hunter T . 1987 Cell 50: 823–829
Jordan P, Matos P, Veríssimo F . 2000 Biochem. Biophys. Res. Commun. 279: 741–743
Knighton DR, Zheng JH, Ten Eyck LF, Ashford VA, Xuong NH, Taylor SS, Sowadski JM . 1991 Science 253: 407–414
Kumar CC . 1998 Oncogene 17: 1365–1373
Liang P, Averboukh L, Pardee AB . 1993 Nucleic Acids Res. 21: 3269–3275
Moore TM, Garg R, Johnson C, Coptcoat MJ, Ridley AJ, Morris JD . 2000 J. Biol. Chem. 275: 4311–4322
Taylor SS, Radzio-Andzelm E, Hunter T . 1995 FASEB J. 9: 1255–1266
Xu B, English JM, Wilsbacher JL, Stippec S, Goldsmith EJ, Cobb MH . 2000 J. Biol. Chem. 275: 16795–16801
Acknowledgements
We thank Sónia Pedro for running the automated ABI sequencer, Bárbara Marques for performing FISH analysis, Eric Chastre, INSERM-U482, Paris for generously providing total RNA from human adult and foetal tissues, Bing-e Xu and Melanie Cobb for sending anti-rat WNK1 serum, and Jonathan Morris for comments on the manuscript. The genomic sequences from clones RP11-388A16 and -359B12 were produced by the Baylor College of Medicine, Texas. This work was supported by the Fundação para a Ciência e Tecnologia, Portugal through grant Praxis/SAU/107/96 and PhD fellowship BD 19936/99 to F. Veríssimo.
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Veríssimo, F., Jordan, P. WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. Oncogene 20, 5562–5569 (2001). https://doi.org/10.1038/sj.onc.1204726
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DOI: https://doi.org/10.1038/sj.onc.1204726
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