serine/threonine protein kinase WNK4;; protein kinase lysine-deficient 4; protein kinase with no lysine 4 (WNK4, PRKWNK4)
Jump to navigation
Jump to search
Function
- serine/threonine protein kinase
- role in regulation of electrolyte homeostasis, cell signaling, cell survival & cell proliferation
- activator of Na+-coupled chloride cotransporters
- inhibitor of K+-coupled chloride cotransporters
- activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 & TRPV6
- regulates activity of thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3
- also inhibits the renal K+ channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of KCNJ1 from the cell surface by clathrin-dependent endocytosis
- WNK4 appears to act as a molecular switch that can vary the balance between Na+ reabsorption & K+ secretion
- phosphorylates NEDD4L
- activation requires autophosphorylation of Ser-335
- phosphorylation of Ser-331 increases activity
- phosphorylated by WNK1 & WNK3 (putative)
- interacts with the C-terminal region of KCNJ1
- interacts with WNK1 & WNK3 (putative)
Structure
- belongs to the protein kinase superfamily, Ser/Thr protein kinase family, WNK subfamily
- contains 1 protein kinase domain
Compartment
- cell junction, tight junction
- present exclusively in intercellular junctions in the distal convoluted tubule & in both the cytoplasm & intercellular junctions in the cortical collecting duct
- WNK4 is part of the tight junction complex (putative)
Alternative splicing
named isoforms=3
Expression
expressed in kidney, colon & skin
Pathology
- defects in WNK4 are a cause of pseudohypoaldosteronism type 2