FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1972808260> ?p ?o ?g. }

• W1972808260 endingPage "15526" @default.
• W1972808260 startingPage "15518" @default.
• W1972808260 abstract "Mutations in the G protein-coupled prokineticin receptor 2 (PKR2) are known to cause Kallmann syndrome and idiopathic hypogonadotropic hypogonadism manifesting with delayed puberty and infertility. Some of the mutant receptors are not routed to the cell surface; instead, they are trapped in the cellular secretory pathway. The cell-permeant agonists/antagonists have been used to rescue some membrane receptors that are not targeted onto the cell membrane. Here, we chose three disease-associated mutations (W178S, G234D, and P290S), which all resulted in retention of PKR2 intracellularly. We show that a small molecule PKR2 antagonist (A457) dramatically increased cell surface expression and rescued the function of P290S PKR2, but had no effect on W178S and G234D PKR2. Furthermore, we also tested chemical chaperone glycerol on the cell surface expression and function of PKR2 mutants. Treatment with 10% glycerol significantly increased the cell surface expression and signaling of P290S and W178S PKR2. These data demonstrate that some Kallmann syndrome-associated, intracellularly retained mutant PKR2 receptors can be functionally rescued, suggesting a potential treatment strategy for patients bearing such mutations. Mutations in the G protein-coupled prokineticin receptor 2 (PKR2) are known to cause Kallmann syndrome and idiopathic hypogonadotropic hypogonadism manifesting with delayed puberty and infertility. Some of the mutant receptors are not routed to the cell surface; instead, they are trapped in the cellular secretory pathway. The cell-permeant agonists/antagonists have been used to rescue some membrane receptors that are not targeted onto the cell membrane. Here, we chose three disease-associated mutations (W178S, G234D, and P290S), which all resulted in retention of PKR2 intracellularly. We show that a small molecule PKR2 antagonist (A457) dramatically increased cell surface expression and rescued the function of P290S PKR2, but had no effect on W178S and G234D PKR2. Furthermore, we also tested chemical chaperone glycerol on the cell surface expression and function of PKR2 mutants. Treatment with 10% glycerol significantly increased the cell surface expression and signaling of P290S and W178S PKR2. These data demonstrate that some Kallmann syndrome-associated, intracellularly retained mutant PKR2 receptors can be functionally rescued, suggesting a potential treatment strategy for patients bearing such mutations." @default.
• W1972808260 created "2016-06-24" @default.
• W1972808260 creator A5045502515 @default.
• W1972808260 creator A5055885693 @default.
• W1972808260 creator A5067431943 @default.
• W1972808260 creator A5075675668 @default.
• W1972808260 creator A5088919481 @default.
• W1972808260 date "2014-05-01" @default.
• W1972808260 modified "2023-10-18" @default.
• W1972808260 title "Functional Rescue of Kallmann Syndrome-associated Prokineticin Receptor 2 (PKR2) Mutants Deficient in Trafficking" @default.
• W1972808260 cites W147981721 @default.
• W1972808260 cites W1501383339 @default.
• W1972808260 cites W1527823690 @default.
• W1972808260 cites W1541573691 @default.
• W1972808260 cites W1970512473 @default.
• W1972808260 cites W1971482162 @default.
• W1972808260 cites W2003282533 @default.
• W1972808260 cites W2004330624 @default.
• W1972808260 cites W2006468022 @default.
• W1972808260 cites W2006662682 @default.
• W1972808260 cites W2023397454 @default.
• W1972808260 cites W2030345298 @default.
• W1972808260 cites W2034975847 @default.
• W1972808260 cites W2035797012 @default.
• W1972808260 cites W2045854255 @default.
• W1972808260 cites W2048782297 @default.
• W1972808260 cites W2058169488 @default.
• W1972808260 cites W2063044361 @default.
• W1972808260 cites W2064752765 @default.
• W1972808260 cites W2071767667 @default.
• W1972808260 cites W2074064220 @default.
• W1972808260 cites W2084612709 @default.
• W1972808260 cites W2085057361 @default.
• W1972808260 cites W2090831400 @default.
• W1972808260 cites W2101968602 @default.
• W1972808260 cites W2104186316 @default.
• W1972808260 cites W2104489981 @default.
• W1972808260 cites W2105458642 @default.
• W1972808260 cites W2111256689 @default.
• W1972808260 cites W2116850492 @default.
• W1972808260 cites W2123745348 @default.
• W1972808260 cites W2128199350 @default.
• W1972808260 cites W2133449590 @default.
• W1972808260 cites W2134049725 @default.
• W1972808260 cites W2135219283 @default.
• W1972808260 cites W2157907012 @default.
• W1972808260 cites W2158061036 @default.
• W1972808260 cites W2160698849 @default.
• W1972808260 cites W2162401422 @default.
• W1972808260 cites W2164691342 @default.
• W1972808260 cites W2167994535 @default.
• W1972808260 cites W2614633882 @default.
• W1972808260 cites W4232529811 @default.
• W1972808260 cites W58091867 @default.
• W1972808260 doi "https://doi.org/10.1074/jbc.m114.556381" @default.
• W1972808260 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4140907" @default.
• W1972808260 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24753254" @default.
• W1972808260 hasPublicationYear "2014" @default.
• W1972808260 type Work @default.
• W1972808260 sameAs 1972808260 @default.
• W1972808260 citedByCount "19" @default.
• W1972808260 countsByYear W19728082602015 @default.
• W1972808260 countsByYear W19728082602016 @default.
• W1972808260 countsByYear W19728082602017 @default.
• W1972808260 countsByYear W19728082602018 @default.
• W1972808260 countsByYear W19728082602020 @default.
• W1972808260 countsByYear W19728082602021 @default.
• W1972808260 countsByYear W19728082602022 @default.
• W1972808260 countsByYear W19728082602023 @default.
• W1972808260 crossrefType "journal-article" @default.
• W1972808260 hasAuthorship W1972808260A5045502515 @default.
• W1972808260 hasAuthorship W1972808260A5055885693 @default.
• W1972808260 hasAuthorship W1972808260A5067431943 @default.
• W1972808260 hasAuthorship W1972808260A5075675668 @default.
• W1972808260 hasAuthorship W1972808260A5088919481 @default.
• W1972808260 hasBestOaLocation W19728082601 @default.
• W1972808260 hasConcept C104317684 @default.
• W1972808260 hasConcept C126322002 @default.
• W1972808260 hasConcept C134018914 @default.
• W1972808260 hasConcept C143065580 @default.
• W1972808260 hasConcept C1491633281 @default.
• W1972808260 hasConcept C170493617 @default.
• W1972808260 hasConcept C2777239080 @default.
• W1972808260 hasConcept C2778106830 @default.
• W1972808260 hasConcept C2779134260 @default.
• W1972808260 hasConcept C2781255401 @default.
• W1972808260 hasConcept C3008058167 @default.
• W1972808260 hasConcept C524204448 @default.
• W1972808260 hasConcept C55493867 @default.
• W1972808260 hasConcept C71315377 @default.
• W1972808260 hasConcept C71924100 @default.
• W1972808260 hasConcept C86803240 @default.
• W1972808260 hasConcept C95444343 @default.
• W1972808260 hasConceptScore W1972808260C104317684 @default.
• W1972808260 hasConceptScore W1972808260C126322002 @default.
• W1972808260 hasConceptScore W1972808260C134018914 @default.
• W1972808260 hasConceptScore W1972808260C143065580 @default.
• W1972808260 hasConceptScore W1972808260C1491633281 @default.

• next