OXSR1
OXSR1 (oxidative stress responsive kinase 1, also known as OSR1 or KIAA1101) is a STE20-family serine/threonine kinase. It acts as the effector of the WNK-SPAK/OSR1 cascade, regulating ion transport, the response to hypertonic stress and blood pressure. Browse Assay Genie's current range of OXSR1 research reagents below, or read on for the biology behind the target.
OXSR1 is the effector serine/threonine-protein kinase of the WNK-SPAK/OSR1 kinase cascade. It acts downstream of the WNK kinases (WNK1, WNK2, WNK3 and WNK4) and, once activated by them, phosphorylates ion cotransporters to regulate their activity. It specifically recognises and binds proteins carrying an RFXV motif, which allows it to engage its substrates and partners.
Its best-characterised targets are members of the SLC12 cotransporter family. Phosphorylation of the Na-K-Cl cotransporters SLC12A1/NKCC2 and SLC12A2/NKCC1 promotes their activation and ion influx. At the same time, phosphorylation of the K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibits them and blocks ion efflux. Through this action OXSR1 mediates regulatory volume increase in response to hyperosmotic stress downstream of WNK1 and WNK3. In the distal convoluted tubule of the kidney, it phosphorylates and activates the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC downstream of WNK4, and so regulates NaCl reabsorption in the distal nephron.
OXSR1 has other roles as well. It regulates angiogenesis in endothelial cells downstream of WNK1. It also activates the inward rectifier potassium channels KCNJ2/Kir2.1 and KCNJ4/Kir2.3 by binding an RXFXV/I motif and controlling their localisation to the cell membrane, without phosphorylating them. Other reported substrates include RELL1, RELL2, RELT and PAK1, and it phosphorylates PLSCR1 in the presence of RELT. NCBI notes that it regulates downstream kinases in response to environmental stress and may help regulate the actin cytoskeleton. The OXSR1 gene belongs to the OXSR1/STK39 kinase family, and the protein sits in the STE20 subfamily of the STE Ser/Thr protein kinase family. Its name derives from the earlier designation oxidative-stress responsive 1.
OXSR1 phosphorylates SLC12 cotransporters, making it a focal point for studying regulatory volume increase and the response to hyperosmotic stress.
Activation of SLC12A3/NCC downstream of WNK4 links OXSR1 to NaCl reabsorption in the distal nephron.
As part of the WNK-SPAK/OSR1 cascade, OXSR1 is implicated in blood pressure control through its effects on ion cotransporters.
OXSR1 acts downstream of WNK1 in endothelial angiogenesis and controls the membrane localisation of Kir2.1 and Kir2.3 potassium channels.
OXSR1 is a serine/threonine kinase that acts downstream of WNK kinases. Once activated, it phosphorylates SLC12 family ion cotransporters, activating Na-K-Cl cotransporters and inhibiting K-Cl cotransporters. This regulates ion transport, the response to hyperosmotic stress and NaCl reabsorption in the kidney.
The HGNC name is oxidative stress responsive kinase 1, with a previous name of oxidative-stress responsive 1. Aliases include OSR1 and KIAA1101, and UniProt lists the protein as serine/threonine-protein kinase OSR1. It belongs to the OXSR1/STK39 kinase family, alongside STK39.
Yes. Mouse and rat both have an ortholog named Oxsr1, so the kinase can be studied in rodent models. Species reactivity differs between reagents, so check the datasheet of any product for its validated reactivity.
Other WNK-SPAK/OSR1 cascade kinases, SLC12 cotransporters, potassium channels and OXSR1 substrates with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O95747; product specifications from Assay Genie datasheets.