Article: article from journal or magazin.
AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway.
Publication types: Journal Article
Elevated catecholamines in the heart evoke transcriptional activation of the Myocyte Enhancer Factor (MEF) pathway to induce a cellular response known as pathological myocardial hypertrophy. We have discovered that the A-Kinase Anchoring Protein (AKAP)-Lbc is upregulated in hypertrophic cardiomyocytes. It coordinates activation and movement of signaling proteins that initiate MEF2-mediated transcriptional reprogramming events. Live-cell imaging, fluorescent kinase activity reporters, and RNA interference techniques show that AKAP-Lbc couples activation of protein kinase D (PKD) with the phosphorylation-dependent nuclear export of the class II histone deacetylase HDAC5. These studies uncover a role for AKAP-Lbc in which increased expression of the anchoring protein selectively amplifies a signaling pathway that drives cardiac myocytes toward a pathophysiological outcome.
14-3-3 Proteins/metabolism, A Kinase Anchor Proteins/genetics, A Kinase Anchor Proteins/metabolism, Active Transport, Cell Nucleus, Animals, COS Cells, Cardiomegaly/metabolism, Cell Line, Cercopithecus aethiops, Cyclic AMP-Dependent Protein Kinases/metabolism, Gene Expression Regulation, Guanine Nucleotide Exchange Factors/genetics, Guanine Nucleotide Exchange Factors/metabolism, Heart Ventricles/drug effects, Histone Deacetylases/metabolism, Humans, Models, Biological, Myocytes, Cardiac/drug effects, Myocytes, Cardiac/metabolism, Myogenic Regulatory Factors/metabolism, Phenylephrine/pharmacology, Phosphorylation, Protein Kinase C/metabolism, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins/metabolism, RNA Interference, Rats, Signal Transduction
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