| http://purl.uniprot.org/citations/26124132 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26124132 | http://www.w3.org/2000/01/rdf-schema#comment | "Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 → Valine) mutation-induced changes in heart morphology and function coincided with largely reduced RLC phosphorylation in situ. We hypothesized that the introduction of a constitutively phosphorylated Serine15 (S15D) into the hearts of D166V mice would prevent the development of a deleterious HCM phenotype. In support of this notion, MLCK-induced phosphorylation of D166V-mutated hearts was found to rescue some of their abnormal contractile properties. Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and morphological assessments. The results were compared with Tg-WT and Tg-D166V mice expressing the human ventricular RLC-WT or its D166V mutant, respectively. Echocardiography and invasive hemodynamic studies demonstrated significant improvements of intact heart function in S15D-D166V mice compared with D166V, with the systolic and diastolic indices reaching those monitored in WT mice. A largely reduced maximal tension and abnormally high myofilament Ca(2+) sensitivity observed in D166V-mutated hearts were reversed in S15D-D166V mice. Low-angle X-ray diffraction study revealed that altered myofilament structures present in HCM-D166V mice were mitigated in S15D-D166V rescue mice. Our collective results suggest that expression of pseudophosphorylated RLC in the hearts of HCM mice is sufficient to prevent the development of the pathological HCM phenotype."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1505819112"xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Huang W."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Liang J."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Yuan C.C."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Irving T.C."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Kazmierczak K."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Hare J.M."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Szczesna-Cordary D."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Kanashiro-Takeuchi R.M."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/author | "Muthu P."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/pages | "E4138-46"xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/title | "Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice."xsd:string |
| http://purl.uniprot.org/citations/26124132 | http://purl.uniprot.org/core/volume | "112"xsd:string |
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