Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Pflugers+Arch 2015 ; 467 (11): 2235-41 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter #MMPMID25904388
Huang CL; Cheng CJ
Pflugers Arch 2015[Nov]; 467 (11): 2235-41 PMID25904388show ga
Mammalian with-no-lysine [K] (WNK) kinases are a family of four serine-threonine protein kinases, WNK1-4. Mutations of WNK1 and WNK4 in humans cause pseudohypoaldosteronism type II (PHA2), an autosomal-dominant disease characterized by hypertension and hyperkalemia. Increased Na+ reabsorption through Na+-Cl? cotransporter NCC in the distal convoluted tubule plays an important role in the pathogenesis of hypertension in patients with PHA2. However, how WNK1 and 4 regulate NCC and how mutations of WNKs cause activation of NCC have been controversial. Here, we review current state of literature supporting a compelling model that WNK1 and WNK4 both contribute to stimulation of NCC. The precise combined effects of WNK1 and WNK4 on NCC remain unclear, but likely are positive rather than antagonistic. The recent discovery that WNK kinases may function as an intracellular chloride sensor adds a new dimension to the physiological role of WNK kinases. Intracellular chloride-dependent regulation of WNK?s may underlie the mechanism of regulation of NCC by extracellular K+. Definite answer yet will require future investigation by tubular perfusion in mice with altered WNK kinase expression.
free
free
free
Pflugers+Arch 2015 ; 467 (11): 2235-41
