STK39
Description
The STK39 (serine/threonine kinase 39) is a protein-coding gene located on chromosome 2.
STK39, also known as STE20/SPS1-related proline-alanine-rich protein kinase, is an enzyme encoded by the STK39 gene in humans. This gene encodes a serine/threonine kinase involved in the cellular stress response pathway. The kinase is activated by hypotonic stress, leading to the phosphorylation of cation-chloride-coupled cotransporters. This kinase specifically activates the p38 MAP kinase pathway, and its interaction with p38 decreases upon cellular stress. Some studies suggest that STK39 might be linked to high blood pressure.
STK39, also known as STE20/SPS1-related proline-alanine-rich protein kinase, DCHT, or Serine/threonine-protein kinase 39, is a serine/threonine-protein kinase that plays a crucial role in the WNK-SPAK/OSR1 kinase cascade. This cascade is involved in various cellular processes including ion transport, response to hypertonic stress, and blood pressure regulation. STK39 specifically recognizes and binds proteins with a RFXV motif. It acts downstream of WNK kinases (WNK1, WNK2, WNK3, or WNK4), becoming activated by these kinases. Once activated, STK39 catalyzes the phosphorylation of ion cotransporters such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2, and SLC12A6/KCC3, ultimately regulating their activity. STK39 is also involved in mediating regulatory volume increase in response to hyperosmotic stress by phosphorylating ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases. The phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 by STK39 promotes their activation and ion influx. Simultaneously, the phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 by STK39 inhibits their activity, blocking ion efflux. Furthermore, STK39 acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of the kidney downstream of WNK4. Additionally, STK39 mediates the inhibition of SLC4A4, SLC26A6, and CFTR activities. It also phosphorylates RELT, and its phosphorylated form forms a complex with WNK2. STK39 interacts with SORL1 via its cytosolic C-terminus.
STK39 is also known as DCHT, PASK, SPAK.
