| http://purl.uniprot.org/citations/19023132 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19023132 | http://www.w3.org/2000/01/rdf-schema#comment | "The sarcomeric titin springs influence myocardial distensibility and passive stiffness. Titin isoform composition and protein kinase (PK)A-dependent titin phosphorylation are variables contributing to diastolic heart function. However, diastolic tone, relaxation speed, and left ventricular extensibility are also altered by PKG activation. We used back-phosphorylation assays to determine whether PKG can phosphorylate titin and affect titin-based stiffness in skinned myofibers and isolated myofibrils. PKG in the presence of 8-pCPT-cGMP (cGMP) phosphorylated the 2 main cardiac titin isoforms, N2BA and N2B, in human and canine left ventricles. In human myofibers/myofibrils dephosphorylated before mechanical analysis, passive stiffness dropped 10% to 20% on application of cGMP-PKG. Autoradiography and anti-phosphoserine blotting of recombinant human I-band titin domains established that PKG phosphorylates the N2-B and N2-A domains of titin. Using site-directed mutagenesis, serine residue S469 near the COOH terminus of the cardiac N2-B-unique sequence (N2-Bus) was identified as a PKG and PKA phosphorylation site. To address the mechanism of the PKG effect on titin stiffness, single-molecule atomic force microscopy force-extension experiments were performed on engineered N2-Bus-containing constructs. The presence of cGMP-PKG increased the bending rigidity of the N2-Bus to a degree that explained the overall PKG-mediated decrease in cardiomyofibrillar stiffness. Thus, the mechanically relevant site of PKG-induced titin phosphorylation is most likely in the N2-Bus; phosphorylation of other titin sites could affect protein-protein interactions. The results suggest that reducing titin stiffness by PKG-dependent phosphorylation of the N2-Bus can benefit diastolic function. Failing human hearts revealed a deficit for basal titin phosphorylation compared to donor hearts, which may contribute to diastolic dysfunction in heart failure."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.org/dc/terms/identifier | "doi:10.1161/circresaha.108.184408"xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "Kruger M."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "Andresen C."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "Redfield M.M."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "Lang P."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "Linke W.A."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "Butt E."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "dos Remedios C.G."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "Kotter S."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/author | "Grutzner A."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/name | "Circ Res"xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/pages | "87-94"xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/title | "Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs."xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://purl.uniprot.org/core/volume | "104"xsd:string |
| http://purl.uniprot.org/citations/19023132 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19023132 |
| http://purl.uniprot.org/citations/19023132 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19023132 |
| http://purl.uniprot.org/uniprot/#_A0A0A0MRA3-mappedCitation-19023132 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19023132 |
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| http://purl.uniprot.org/uniprot/#_A0A0C4DG59-mappedCitation-19023132 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19023132 |
| http://purl.uniprot.org/uniprot/#_A2TKE3-mappedCitation-19023132 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19023132 |
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| http://purl.uniprot.org/uniprot/#_A2TKE5-mappedCitation-19023132 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19023132 |