FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2048337652> ?p ?o ?g. }

• W2048337652 endingPage "231" @default.
• W2048337652 startingPage "223" @default.
• W2048337652 abstract "The SPAK (STE20/SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase-1) kinases interact and phosphorylate NKCC1 (Na+–K+–2Cl− co-transporter-1), leading to its activation. Recent studies indicated that SPAK and OSR1 are phosphorylated and activated by the WNK1 [with no K (lysine) protein kinase-1] and WNK4, genes mutated in humans affected by Gordon's hypertension syndrome. In the present study, we have identified three residues in NKCC1 (Thr175/Thr179/Thr184 in shark or Thr203/Thr207/Thr212 in human) that are phosphorylated by SPAK and OSR1, and have developed a peptide substrate, CATCHtide (cation chloride co-transporter peptide substrate), to assess SPAK and OSR1 activity. Exposure of HEK-293 (human embryonic kidney) cells to osmotic stress, which leads to phosphorylation and activation of NKCC1, increased phosphorylation of NKCC1 at the sites targeted by SPAK/OSR1. The residues on NKCC1, phosphorylated by SPAK/OSR1, are conserved in other cation co-transporters, such as the Na+–Cl− co-transporter, the target of thiazide drugs that lower blood pressure in humans with Gordon's syndrome. Furthermore, we characterize the properties of a 92-residue CCT (conserved C-terminal) domain on SPAK and OSR1 that interacts with an RFXV (Arg-Phe-Xaa-Val) motif present in the substrate NKCC1 and its activators WNK1/WNK4. A peptide containing the RFXV motif interacts with nanomolar affinity with the CCT domains of SPAK/OSR1 and can be utilized to affinity-purify SPAK and OSR1 from cell extracts. Mutation of the arginine, phenylalanine or valine residue within this peptide abolishes binding to SPAK/OSR1. We have identified specific residues within the CCT domain that are required for interaction with the RFXV motif and have demonstrated that mutation of these in OSR1 inhibited phosphorylation of NKCC1, but not of CATCHtide which does not possess an RFXV motif. We establish that an intact CCT domain is required for WNK1 to efficiently phosphorylate and activate OSR1. These data establish that the CCT domain functions as a multipurpose docking site, enabling SPAK/OSR1 to interact with substrates (NKCC1) and activators (WNK1/WNK4)." @default.
• W2048337652 created "2016-06-24" @default.
• W2048337652 creator A5013216604 @default.
• W2048337652 creator A5016013198 @default.
• W2048337652 creator A5025905669 @default.
• W2048337652 creator A5028009861 @default.
• W2048337652 creator A5029912474 @default.
• W2048337652 creator A5036426250 @default.
• W2048337652 creator A5054181982 @default.
• W2048337652 date "2006-06-14" @default.
• W2048337652 modified "2023-10-18" @default.
• W2048337652 title "Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1" @default.
• W2048337652 cites W111392919 @default.
• W2048337652 cites W1552509407 @default.
• W2048337652 cites W1973469920 @default.
• W2048337652 cites W1975016763 @default.
• W2048337652 cites W1996423252 @default.
• W2048337652 cites W1996856159 @default.
• W2048337652 cites W2019326144 @default.
• W2048337652 cites W2024936138 @default.
• W2048337652 cites W2049277771 @default.
• W2048337652 cites W2052539926 @default.
• W2048337652 cites W2053936821 @default.
• W2048337652 cites W2109073510 @default.
• W2048337652 cites W2123307919 @default.
• W2048337652 cites W2131510524 @default.
• W2048337652 cites W2142766228 @default.
• W2048337652 cites W2150380575 @default.
• W2048337652 cites W2409907282 @default.
• W2048337652 doi "https://doi.org/10.1042/bj20060220" @default.
• W2048337652 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1479760" @default.
• W2048337652 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16669787" @default.
• W2048337652 hasPublicationYear "2006" @default.
• W2048337652 type Work @default.
• W2048337652 sameAs 2048337652 @default.
• W2048337652 citedByCount "266" @default.
• W2048337652 countsByYear W20483376522012 @default.
• W2048337652 countsByYear W20483376522013 @default.
• W2048337652 countsByYear W20483376522014 @default.
• W2048337652 countsByYear W20483376522015 @default.
• W2048337652 countsByYear W20483376522016 @default.
• W2048337652 countsByYear W20483376522017 @default.
• W2048337652 countsByYear W20483376522018 @default.
• W2048337652 countsByYear W20483376522019 @default.
• W2048337652 countsByYear W20483376522020 @default.
• W2048337652 countsByYear W20483376522021 @default.
• W2048337652 countsByYear W20483376522022 @default.
• W2048337652 countsByYear W20483376522023 @default.
• W2048337652 crossrefType "journal-article" @default.
• W2048337652 hasAuthorship W2048337652A5013216604 @default.
• W2048337652 hasAuthorship W2048337652A5016013198 @default.
• W2048337652 hasAuthorship W2048337652A5025905669 @default.
• W2048337652 hasAuthorship W2048337652A5028009861 @default.
• W2048337652 hasAuthorship W2048337652A5029912474 @default.
• W2048337652 hasAuthorship W2048337652A5036426250 @default.
• W2048337652 hasAuthorship W2048337652A5054181982 @default.
• W2048337652 hasBestOaLocation W20483376522 @default.
• W2048337652 hasConcept C104317684 @default.
• W2048337652 hasConcept C11960822 @default.
• W2048337652 hasConcept C149011108 @default.
• W2048337652 hasConcept C170493617 @default.
• W2048337652 hasConcept C178790620 @default.
• W2048337652 hasConcept C184235292 @default.
• W2048337652 hasConcept C185592680 @default.
• W2048337652 hasConcept C188053792 @default.
• W2048337652 hasConcept C2910050888 @default.
• W2048337652 hasConcept C537181965 @default.
• W2048337652 hasConcept C55493867 @default.
• W2048337652 hasConcept C86803240 @default.
• W2048337652 hasConcept C88045685 @default.
• W2048337652 hasConcept C95444343 @default.
• W2048337652 hasConcept C97029542 @default.
• W2048337652 hasConceptScore W2048337652C104317684 @default.
• W2048337652 hasConceptScore W2048337652C11960822 @default.
• W2048337652 hasConceptScore W2048337652C149011108 @default.
• W2048337652 hasConceptScore W2048337652C170493617 @default.
• W2048337652 hasConceptScore W2048337652C178790620 @default.
• W2048337652 hasConceptScore W2048337652C184235292 @default.
• W2048337652 hasConceptScore W2048337652C185592680 @default.
• W2048337652 hasConceptScore W2048337652C188053792 @default.
• W2048337652 hasConceptScore W2048337652C2910050888 @default.
• W2048337652 hasConceptScore W2048337652C537181965 @default.
• W2048337652 hasConceptScore W2048337652C55493867 @default.
• W2048337652 hasConceptScore W2048337652C86803240 @default.
• W2048337652 hasConceptScore W2048337652C88045685 @default.
• W2048337652 hasConceptScore W2048337652C95444343 @default.
• W2048337652 hasConceptScore W2048337652C97029542 @default.
• W2048337652 hasIssue "1" @default.
• W2048337652 hasLocation W20483376521 @default.
• W2048337652 hasLocation W20483376522 @default.
• W2048337652 hasLocation W20483376523 @default.
• W2048337652 hasLocation W20483376524 @default.
• W2048337652 hasLocation W20483376525 @default.
• W2048337652 hasLocation W20483376526 @default.
• W2048337652 hasOpenAccess W2048337652 @default.
• W2048337652 hasPrimaryLocation W20483376521 @default.
• W2048337652 hasRelatedWork W1520436089 @default.
• W2048337652 hasRelatedWork W1837849234 @default.

• next