OSR1 predesign siRNA
- Known as:
- OSR1 predesign small interfearing RNA
- Catalog number:
- RI13765
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- OSR1 predesign siRNA
Related genes to: OSR1 predesign siRNA
- Gene:
- OSR1 NIH gene
- Name:
- odd-skipped related transcription factor 1
- Previous symbol:
- ODD
- Synonyms:
- -
- Chromosome:
- 2p24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-11-14
- Date modifiied:
- 2018-11-05
- Gene:
- OXSR1 NIH gene
- Name:
- oxidative stress responsive kinase 1
- Previous symbol:
- OSR1
- Synonyms:
- KIAA1101
- Chromosome:
- 3p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-06
- Date modifiied:
- 2018-10-15
Related products to: OSR1 predesign siRNA
Related articles to: OSR1 predesign siRNA
- Life depends on maintaining water homeostasis and internal osmolality constancy. In terrestrial animals, the release of the antidiuretic hormone arginine vasopressin (AVP) in response to variations of extracellular osmolality (tonicity) is crucial. We have reported that WNK1 kinase in the vascular-organ-of-lamina-terminalis (OVLT) nuclei of the brain mediates the hypertonicity-induced AVP release by activating the voltage-gated K channel Kv3.1 increasing action potential firing. The downstream mechanism for WNK1-mediated osmosensation is unknown. Here, we showed that the hypertonicity-induced increases in Kv3.1 currents in cultured cells required the oxidative stress-responsive-1 (OSR1) or STE20/SPS1-related proline/alanine-rich (SPAK) kinase. Both kinases were present in the mouse OVLT area. Hypertonicity induced by water restriction or mannitol injection increased the abundance of phosphorylated OSR1 and SPAK in the OVLT. Double deletion of Osr1 and Spak in the OVLT in mice caused polyuria with relative hypotonic urine that persisted in water restriction. The water restriction-induced AVP release was blunted in Osr1 and Spak-deleted mice. In brain slice recordings, the hypertonicity-induced increases in action potential firing in OVLT were blunted by Osr1 and Spak deletion. Deletion of the Kv3.1 channel in the OVLT showed a similar phenotype. Expression of the constitutively active OSR1 in the OVLT resulted in increased AVP release and inappropriate antidiuretic hormone secretion phenotype. In summary, OSR1/SPAK acts downstream of WNK1 to regulate AVP release in response to hypertonicity. In OVLT neurons OSR1/SPAK activates Kv3.1 to increase action potential firing. Thus, the WNK1-OSR1/SPAK-Kv3.1 cascade regulates water homeostasis and AVP release to control osmolality stability. - Source: PubMed
Jin XinXie JianYeh Chia-WeiLi Yu-JuiLien Cheng-ChangHuang Chou-Long - The WNK-OSR1/SPAK protein kinase pathway regulates ion homeostasis and cell volume, but its other functions are not well understood. To discover undefined signaling functions, we utilized experimentally-derived binding specificity to predict interactions and relative affinities with the conserved C-terminal (CCT) domains of OSR1 and SPAK, which bind short linear motifs. The upstream kinases WNKs 1-4 and their relatives, the pseudokinases NRBP1/2, also contain CCT-like domains which have conserved folds and motif binding pockets. Motifs were scored using peptide arrays, conservation, cytosolic localization, and solvent accessibility. Out of nearly 3700 motifs in the human proteome, 90% of previously published motifs ranked in the top 2% of those predicted. Interactions with selected candidates, including TSC22D1 and CAVIN1, were validated, and their localization and/or modifications were coupled to changes in WNK1 signaling. We also identified additional motif variants and confirmed binding to the NRBP1 CCT-like domain. Our results stress the diverse functionality of CCT/CCT-like domains and implicates unexpected interactions driving WNK biology. - Source: PubMed
Publication date: 2025/09/05
Taylor Clinton AJung Ji-UngGallolu Kankanamalage SachithLi JustinGrzemska MagdalenaJaykumar Ankita BEarnest SvetlanaStippec SteveSaha PurbitaSauceda EustoliaCobb Melanie H - With No lysine (K) 1 (WNK1) is essential for ion and volume homeostasis, sensing osmotic stress and activating pathways that regulate ion transport. Its response to osmotic stress shares similarities with the function of the mechanosensitive ion channel Piezo1. In this study, we show that Yoda1, a Piezo1 agonist, activates WNK1 downstream kinase targets oxidative stress-responsive 1 (OSR1) and STE20/SPS1-related serine, proline-, and alanine-rich kinase (SPAK) in endothelial cells within minutes. Ionophore-induced Ca influx similarly triggers their activation. Comparable responses were observed in HDMEC, HUVEC, A549, MDA-MB-231, and HeLa cells. Hypotonic stress also enhances SPAK and OSR1 phosphorylation, which is attenuated by WNK1 inhibition or Piezo1 knockdown, whereas hypertonic stress-induced phosphorylation is not affected by Piezo1 knockdown. Chelating Ca or depleting intracellular stores prevents their activation, while increasing intracellular Ca via the Na/Ca exchanger or thapsigargin enhances it. ER-released Ca is sufficient to activate SPAK and OSR1 even in the absence of extracellular Ca, and this effect is diminished by Piezo1 knockdown. Both Yoda1 and ionomycin promote phosphorylation of WNK1 at serine 382, a modification that increases its catalytic activity. These findings identify Piezo1 as an activator of WNK1, linking Ca dynamics to WNK1-OSR1/SPAK signaling. - Source: PubMed
Publication date: 2025/08/29
Jung Ji-UngStippec SteveCobb Melanie H - Uterine spiral artery remodeling (uSAR) is a hallmark of hemochorial placentation. Compromised uSAR leads to adverse pregnancy outcomes. Salient developmental events involved in uSAR are active areas of research and include (a) trophendothelial cell invasion into the spiral arteries, selected demise of endothelial cells; (b) de-differentiation of vascular smooth muscle cells (VSMC); and (c) migration and/or death of VSMCs surrounding spiral arteries. Here we demonstrated that cellular prion (PRNP) is expressed in the rat metrial gland, the entry point of spiral arteries with the highest expression on E16.5, the day at which trophoblast invasion peaks. PRNP is expressed in VSMCs that drift away from the arterial wall. RNA interference of Prnp functionally restricted migration and invasion of rat VSMCs. Furthermore, PRNP interacted with two migration-promoting factors, focal adhesion kinase (FAK) and platelet-derived growth factor receptor-β (PDGFR-β), forming a ter-molecular complex in both the metrial gland and A7r5 cells. The presence of multiple putative binding site of odd skipped related-1 (OSR1) transcription factor on the Prnp promoter was observed using in silico promoter analysis. Ectopic overexpression of OSR1 increased, and knockdown of OSR1 decreased expression of PRNP in VSMCs. Coculture of VSMCs with rat primary trophoblast cells decreased the levels of OSR1 and PRNP. Interestingly, PRNP knockdown led to apoptotic death in ~9% of VSMCs and activated extrinsic apoptotic pathways. PRNP interacts with TRAIL-receptor DR4 and protects VSMCs from TRAIL-mediated apoptosis. These results highlight the biological functions of PRNP in VSMC cell-fate determination during uteroplacental development, an important determinant of healthy pregnancy outcome. - Source: PubMed
Publication date: 2023/10/11
Bose RumelaJana Sarmita SanjayAin Rupasri - STE20/SPS1-related proline/alanine-rich kinase (SPAK) and oxidative stress responsive 1 (OSR1) kinase are two serine/threonine protein kinases that regulate the function of ion co-transporters through phosphorylation. The highly conserved C-terminal (CCT) domains of SPAK and OSR1 bind to RFx[V/I] peptide sequences from their upstream 'With No Lysine Kinases (WNKs), facilitating their activation via phosphorylation. Thus, the inhibition of SPAK and OSR1 binding, via their CCT domains, to WNK kinases is a plausible strategy for inhibiting SPAK and OSR1 kinases. To facilitate structure-guided drug design of such inhibitors, we expressed and purified human SPAK and OSR1 CCT domains and solved their crystal structures. Interestingly, these crystal structures show a highly conserved primary pocket adjacent to a flexible secondary pocket. We also employed a biophysical strategy and determined the affinity of SPAK and OSR1 CCT domains to short peptides derived from WNK4 and NKCC1. Together, this work provides a platform that facilitates the design of CCT domain specific small molecule binders that inhibit SPAK- and OSR1-activation by WNK kinases, and these could be useful in treating hypertension and ischemic stroke. - Source: PubMed
Publication date: 2021/11/24
Elvers Karen TLipka-Lloyd MagdalenaTrueman Rebecca CBax Benjamin DMehellou Youcef