| http://purl.uniprot.org/citations/17431507 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17431507 | http://www.w3.org/2000/01/rdf-schema#comment | "Studies with isolated membrane fractions have shown that calmodulin (CaM) inhibits the activity of cardiac muscle cell Ca(2+) release channel ryanodine receptor 2 (RyR2). To determine the physiological importance of CaM regulation of RyR2, we generated a mouse with 3 amino acid substitutions (RyR2-W3587A/L3591D/F3603A) in exon 75 of the Ryr2 gene, which encodes the CaM-binding site of RyR2. Homozygous mutant mice showed an increased ratio of heart weight to body weight, greatly reduced fractional shortening of the left ventricle, and lethality at 9-16 days of age. Biochemical analysis of hearts of 7- and 10-day-old homozygous mutant mice indicated an impaired CaM inhibition of RyR2 at micromolar Ca(2+) concentrations, reduction in RyR2 protein levels and sarcoplasmic reticulum Ca(2+) sequestration, and upregulation of genes and/or proteins associated with class II histone deacetylase/myocyte enhancer factor-2 and calcineurin signaling pathways. Sustained Ca(2+) transients, often displaying repeated periods of incomplete Ca(2+) removal, were observed in homozygous cardiomyocytes. Taken together, the data indicate that impaired CaM inhibition of RyR2, associated with defective sarcoplasmic reticulum Ca(2+) release and altered gene expression, leads to cardiac hypertrophy and early death."xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci29515"xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/author | "Xu L."xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/author | "Takahashi N."xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/author | "Smithies O."xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/author | "Yamaguchi N."xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/author | "Meissner G."xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/pages | "1344-1353"xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/title | "Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac muscle Ca release channel."xsd:string |
| http://purl.uniprot.org/citations/17431507 | http://purl.uniprot.org/core/volume | "117"xsd:string |
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