WNK1: analysis of protein kinase structure, downstream targets, and potential roles in hypertension.
The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.
Xu
Bing E
BE
Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, USA. melanie.cobb@UTSouthwestern.edu
Lee
Byung Hoon
BH
Min
Xiaoshan
X
Lenertz
Lisa
L
Heise
Charles J
CJ
Stippec
Steve
S
Goldsmith
Elizabeth J
EJ
Cobb
Melanie H
MH
D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000378:metabolism; D004573:Electrolytes; D004789:Enzyme Activation; D017353:Gene Deletion; D015723:Gene Library; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011546:Pseudohypoaldosteronism / Q000235:genetics; D034622:RNA Interference; D050857:Synaptotagmins; D020798:Two-Hybrid System Techniques; D000076204:WNK Lysine-Deficient Protein Kinase 1
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D004573:Electrolytes; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; D050857:Synaptotagmins; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human; D048054:Mitogen-Activated Protein Kinase 7