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

We have cloned and characterized a novel human serine/ threonine protein ki nase gene from chromosome 12p13.3 encoding 2382 amino acids. Remarkably, th e catalytic domain sequence contains a cysteine in place of a lysine residu e 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 ne arby 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 d escribed human kinase which we have called human WNK1. The WNK1 catalytic d omain has closest homology with human PAK2, MEKK3, and Raf-1. Three additio nal, 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 gene s, all exclusively from multicellular organisms, which share a WNK kinase s equence signature within subdomains I and II of the catalytic domain. We su ggest that they constitute a novel subfamily of protein kinases that evolve d together with cell adhesion and tissue-formation.