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Data demonstrate that hypotonic low-chloride conditions that activate the WNK1-SPAK and OSR1 pathway promote phosphorylation of NKCC2 isoforms.
OSR1 and SPAK integrate signals from osmosensing and survival pathways.
our data show a novel role for the WNK1/OSR1/NKCC1 pathway in glioma migration
SPAK and OSR1 are powerful negative regulators of the cell volume regulatory Cl- channel ClC-2
study identifies a separation of functions for the WNK1-activated protein kinases OSR1 and SPAK in mediating proliferation, invasion, and gene expression in endothelial cells
The CCT domain directly interacts with the kinase domain to block substrate access and inhibit the domain-swapped homodimerization of the kinase domain of OSR1.
WNK 1, 3, 4, OSR1, and SPAK signaling system known to play a role in regulating the phosphorylation status, and hence activity of the CCCs in other tissues, is also present in the rat and human lenses.
OSR1 has the capacity to downregulate the peptide transporters PEPT1 and PEPT2 by decreasing the carrier protein abundance in the cell membrane
Both, SPAK and OSR1, are negative regulators of the creatine transporter SLC6A8
SPAK and OSR1 are negative regulators of EAAT3 activity
SPAK and OSR1 are powerful negative regulators of the excitatory glutamate transporters EAAT1 and EAAT2.
SPAK and OSR1 are powerful stimulators of the intestinal Na+-coupled phosphate co-transporter NaPi-IIb
OSR1 protein has both the potential to up-regulate KCNQ1/E1 protein abundance in the cell membrane, an effect possibly participating in the regulation of cell volume, excitability, epithelial transport and metabolism.
SPAK and OSR1 are both stimulators of Kir2.1 activity.
Both SPAK and OSR1 kinases entering cells through exosomes are preferentially expressed at the plasma membrane and that the kinases in exosomes are functional and maintain NKCC1 in a phosphorylated state.
the WNK-regulated SPAK/OSR1 kinases directly phosphorylate the N[K]CCs and KCCs, promoting their stimulation and inhibition respectively.
SPAK and OSR1, which are often coexpressed in cells, can form functional heterodimers.
Data show that intracellular association between WNK1 and oxidative stress-responsive 1 (OSR1) is required for stimulation of OSR1 and Na(+), K(+), Cl(-)-Cotransporter NKCC1 and NKCC2 activities by osmotic stress.
OXSR1 and WNK3 transcripts were substantially overexpressed in subjects with schizophrenia relative to comparison subjects.
interacts with cation chloride cotransporters
increased phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter in obesity and identifies a new role for AMP-activated protein kinase in regulating the activity of oxidative stress responsive 1 kinase-related proline-alanine-rich protein kinase
OSR1 is expressed in intestine and partial WNK insensitivity of OSR1 increases intestinal Na( )/H( ) exchanger activity and colonic epithelium Na( ) channel activity
Data indicate that SPAK and OSR1 function interdependently in the distal convoluted tubule (DCT) to positively regulate thiazide-sensitive sodium-chloride cotransporter, NCC.
Partial OSR1 deficiency influences Na(+)/H(+) exchanger activity, ROS formation, and migration of dendritic cells.
Results clearly establish that PHAII caused by the WNK4 D561A mutation is dependent on the activation of the WNK-OSR1/SPAK-NCC cascade.
Two Ste20-like kinases that bind and phosphorylate NKCC1: Ste20-related proline-alanine-rich kinase (SPAK) and oxidative-stress response 1 (OSR1), were identified.
In the kidneys, NKCC2 but not NCC is the main target of OSR1 and the reduced p-NKCC2 in KSP-OSR1(-/-) mice may lead to a Bartter-like syndrome.
phosphorylation states of NCC and OSR1/SPAK (Gene: Oxsr1, GeneID: 108737) were increased by low-salt diets and decreased by high-salt diets
OSR1, a kinase closely related to SPAK, exhibited similar kinase properties and similar functional activation of NKCC1 when coexpressed with WNK4.
review: NCC in the distal convoluted tubule plays a critical role in NaCl and, indirectly, in K+ homeostasis; regulation by SPAK/OSR1 kinases and WNKs.
The gene shows 92.8% nucleotide identity and 95.5% amino acid identity with human OSR1.
The product of this gene belongs to the Ser/Thr protein kinase family of proteins. It regulates downstream kinases in response to environmental stress, and may play a role in regulating the actin cytoskeleton.
oxidative stress-responsive 1 protein
, oxidative-stress responsive 1
, serine/threonine-protein kinase OSR1
, oxidative stress-responsive 1
, oxidative stress-responsive protein 1
, oxidative stress-responsive serine-rich protein 1
, peroxide-inducible transcript 1 protein