RGD Reference Report - A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart. - Rat Genome Database

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A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart.

Authors: Seguchi, O  Takashima, S  Yamazaki, S  Asakura, M  Asano, Y  Shintani, Y  Wakeno, M  Minamino, T  Kondo, H  Furukawa, H  Nakamaru, K  Naito, A  Takahashi, T  Ohtsuka, T  Kawakami, K  Isomura, T  Kitamura, S  Tomoike, H  Mochizuki, N  Kitakaze, M 
Citation: Seguchi O, etal., J Clin Invest. 2007 Oct;117(10):2812-24.
RGD ID: 8554371
Pubmed: (View Article at PubMed) PMID:17885681
DOI: Full-text: DOI:10.1172/JCI30804

Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing human myocardium. Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v), which is involved in the development of human cardiomyopathy, is an important structural protein that affects physiologic cardiac sarcomere formation and heart development. Integrated cDNA expression analysis of failing human myocardia uncovered a novel protein kinase, cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. Expression levels of cardiac-MLCK were well correlated with the pulmonary arterial pressure of patients with heart failure. In cultured cardiomyocytes, knockdown of cardiac-MLCK by specific siRNAs decreased MLC2v phosphorylation and impaired epinephrine-induced activation of sarcomere reassembly. To further clarify the physiologic roles of cardiac-MLCK in vivo, we cloned the zebrafish ortholog z-cardiac-MLCK. Knockdown of z-cardiac-MLCK expression using morpholino antisense oligonucleotides resulted in dilated cardiac ventricles and immature sarcomere structures. These results suggest a significant role for cardiac-MLCK in cardiogenesis.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component
cytosol  (IDA)

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Mylk3  (myosin light chain kinase 3)


Additional Information