FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313311915> ?p ?o ?g. }

• W4313311915 abstract "Background: PKA (protein kinase A)–mediated phosphorylation of cardiac RyR2 (ryanodine receptor 2) has been extensively studied for decades, but the physiological significance of PKA phosphorylation of RyR2 remains poorly understood. Recent determination of high-resolution 3-dimensional structure of RyR2 in complex with CaM (calmodulin) reveals that the major PKA phosphorylation site in RyR2, serine-2030 (S2030), is located within a structural pathway of CaM-dependent inactivation of RyR2. This novel structural insight points to a possible role of PKA phosphorylation of RyR2 in CaM-dependent inactivation of RyR2, which underlies the termination of Ca 2+ release and induction of cardiac Ca 2+ alternans. Methods: We performed single-cell endoplasmic reticulum Ca 2+ imaging to assess the impact of S2030 mutations on Ca 2+ release termination in human embryonic kidney 293 cells. Here we determined the role of the PKA site RyR2-S2030 in a physiological setting, we generated a novel mouse model harboring the S2030L mutation and carried out confocal Ca 2+ imaging. Results: We found that mutations, S2030D, S2030G, S2030L, S2030V, and S2030W reduced the endoplasmic reticulum luminal Ca 2+ level at which Ca 2+ release terminates (the termination threshold), whereas S2030P and S2030R increased the termination threshold. S2030A and S2030T had no significant impact on release termination. Furthermore, CaM–wild-type increased, whereas Ca 2+ binding deficient CaM mutant (CaM-M [a loss-of-function CaM mutation with all 4 EF-hand motifs mutated]), PKA, and Ca 2+ /CaMKII (CaM-dependent protein kinase II) reduced the termination threshold. The S2030L mutation abolished the actions of CaM–wild-type, CaM-M, and PKA, but not CaMKII, in Ca 2+ release termination. Moreover, we showed that isoproterenol and CaM-M suppressed pacing-induced Ca 2+ alternans and accelerated Ca 2+ transient recovery in intact working hearts, whereas CaM–wild-type exerted an opposite effect. The impact of isoproterenol was partially and fully reversed by the PKA inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide and the CaMKII inhibitor N-[2-[N-(4-chlorocinnamyl)-N-methylaminomethyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide individually and together, respectively. S2030L abolished the impact of CaM–wild-type, CaM-M, and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide–sensitive component, but not the N-[2-[N-(4-chlorocinnamyl)-N-methylaminomethyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide–sensitive component, of isoproterenol." @default.
• W4313311915 created "2023-01-06" @default.
• W4313311915 creator A5010523668 @default.
• W4313311915 creator A5011929708 @default.
• W4313311915 creator A5018496827 @default.
• W4313311915 creator A5036991580 @default.
• W4313311915 creator A5061065349 @default.
• W4313311915 creator A5062814947 @default.
• W4313311915 creator A5065941768 @default.
• W4313311915 creator A5066932194 @default.
• W4313311915 creator A5073392743 @default.
• W4313311915 creator A5078207017 @default.
• W4313311915 date "2023-01-20" @default.
• W4313311915 modified "2023-09-30" @default.
• W4313311915 title "RyR2 Serine-2030 PKA Site Governs Ca ²⁺ Release Termination and Ca ²⁺ Alternans" @default.
• W4313311915 cites W1515283778 @default.
• W4313311915 cites W1594174489 @default.
• W4313311915 cites W1966467373 @default.
• W4313311915 cites W1972230645 @default.
• W4313311915 cites W1973228369 @default.
• W4313311915 cites W1977252918 @default.
• W4313311915 cites W1978985432 @default.
• W4313311915 cites W1983710068 @default.
• W4313311915 cites W1992091268 @default.
• W4313311915 cites W1993155483 @default.
• W4313311915 cites W2009775227 @default.
• W4313311915 cites W2010781827 @default.
• W4313311915 cites W2014917932 @default.
• W4313311915 cites W2020083803 @default.
• W4313311915 cites W2026789606 @default.
• W4313311915 cites W2029620282 @default.
• W4313311915 cites W2031053544 @default.
• W4313311915 cites W2047666915 @default.
• W4313311915 cites W2050584736 @default.
• W4313311915 cites W2050824263 @default.
• W4313311915 cites W2051165347 @default.
• W4313311915 cites W2059254718 @default.
• W4313311915 cites W2060913542 @default.
• W4313311915 cites W2072471403 @default.
• W4313311915 cites W2082633743 @default.
• W4313311915 cites W2086449013 @default.
• W4313311915 cites W2086817408 @default.
• W4313311915 cites W2089936541 @default.
• W4313311915 cites W2101742222 @default.
• W4313311915 cites W2111954747 @default.
• W4313311915 cites W2119956887 @default.
• W4313311915 cites W2120618720 @default.
• W4313311915 cites W2122638396 @default.
• W4313311915 cites W2124941830 @default.
• W4313311915 cites W2125802188 @default.
• W4313311915 cites W2129774784 @default.
• W4313311915 cites W2129968803 @default.
• W4313311915 cites W2137283585 @default.
• W4313311915 cites W2138691660 @default.
• W4313311915 cites W2141260882 @default.
• W4313311915 cites W2141646835 @default.
• W4313311915 cites W2145563296 @default.
• W4313311915 cites W2147510951 @default.
• W4313311915 cites W2149061128 @default.
• W4313311915 cites W2153066829 @default.
• W4313311915 cites W2154620339 @default.
• W4313311915 cites W2159453909 @default.
• W4313311915 cites W2160907082 @default.
• W4313311915 cites W2163884090 @default.
• W4313311915 cites W2166325927 @default.
• W4313311915 cites W2166529567 @default.
• W4313311915 cites W2167339045 @default.
• W4313311915 cites W2168013049 @default.
• W4313311915 cites W2334859129 @default.
• W4313311915 cites W2340144859 @default.
• W4313311915 cites W2509451263 @default.
• W4313311915 cites W2531604887 @default.
• W4313311915 cites W2587412607 @default.
• W4313311915 cites W2834279661 @default.
• W4313311915 cites W2904362325 @default.
• W4313311915 cites W2920322147 @default.
• W4313311915 cites W3009875259 @default.
• W4313311915 cites W3010459846 @default.
• W4313311915 cites W30756424 @default.
• W4313311915 cites W3114933038 @default.
• W4313311915 cites W3135071269 @default.
• W4313311915 cites W3184532391 @default.
• W4313311915 cites W4220967680 @default.
• W4313311915 cites W4233503959 @default.
• W4313311915 doi "https://doi.org/10.1161/circresaha.122.321177" @default.
• W4313311915 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36583384" @default.
• W4313311915 hasPublicationYear "2023" @default.
• W4313311915 type Work @default.
• W4313311915 citedByCount "2" @default.
• W4313311915 countsByYear W43133119152023 @default.
• W4313311915 crossrefType "journal-article" @default.
• W4313311915 hasAuthorship W4313311915A5010523668 @default.
• W4313311915 hasAuthorship W4313311915A5011929708 @default.
• W4313311915 hasAuthorship W4313311915A5018496827 @default.
• W4313311915 hasAuthorship W4313311915A5036991580 @default.
• W4313311915 hasAuthorship W4313311915A5061065349 @default.
• W4313311915 hasAuthorship W4313311915A5062814947 @default.
• W4313311915 hasAuthorship W4313311915A5065941768 @default.
• W4313311915 hasAuthorship W4313311915A5066932194 @default.
• W4313311915 hasAuthorship W4313311915A5073392743 @default.

• next