Nudge-nudge, WNK-WNK (kinases), say no more?

Contents Summary 35 I Overview of animal and plant WNK kinases 35 II. Structure: domains and topology 36 III. Phylogeny-evolutionary relationships 41 IV. Plant WNK kinase distribution and regulation of WNK expression and activity 41 V. Functions of WNK family members in physiology and development 41 VI. Say no more? Still many questions to be answered 45 Acknowledgements 46 References 46 SUMMARY: WITH NO LYSINE (WNK) kinases are serine/threonine kinases uniquely characterized by an anomalous placement of a catalytic lysine, hence their moniker. In animals, WNK protein kinases play critical roles in protein trafficking of components that mediate renal ion transport processes and regulate osmoregulation of cell volume. In plants, the WNK kinase gene family is larger and more diverse. Recent studies revealed WNK kinase roles in orchestrating the trafficking of an ion channel, a lipid kinase complex in animals, and a heterotrimeric G protein signaling component in plants that is necessary for signal transduction. For this reason, new attention is geared toward investigating the mechanisms adopted by WNK kinases to nudge intracellular proteins to their destinations. In this review, the functions of WNK kinases in protein trafficking are derived from what we have learned from the model organism Arabidopsis thaliana. To place this new idea in context, we provide the predicted WNK kinase structures, their predicted expression patterns, a speculated evolutionary pathway, and the regulatory roles of plant WNKs in transport processes and other physiologies. We brazenly predict that the WNK kinases in both plants and animals will soon be recognized as a nexus for trafficking-based signal transduction.