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WNK kinases, a novel protein kinase subfamily in multi-cellular organisms

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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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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Correspondence to Peter Jordan.

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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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