AKAP-Lbc Mobilizes a Cardiac Hypertrophy Signaling Pathway
Copyright policy )AKAP-Lbc Mobilizes a Cardiac Hypertrophy Signaling Pathway
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.
- University of Lausanne Switzerland
- Oregon Health & Science University United States
- Howard Hughes Medical Institute United States
- University of California, San Diego United States
- University of Colorado Anschutz Medical Campus United States
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, Heart Ventricles, Active Transport, Cell Nucleus, A Kinase Anchor Proteins, Cardiomegaly, Models, Biological, Histone Deacetylases, Cell Line, Minor Histocompatibility Antigens, Phenylephrine, Chlorocebus aethiops, Animals, Guanine Nucleotide Exchange Factors, Humans, Myocytes, Cardiac, Molecular Biology, MEF2 Transcription Factors, Cell Biology, Cyclic AMP-Dependent Protein Kinases, 14-3-3 Proteins, Gene Expression Regulation, Myogenic Regulatory Factors, COS Cells
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, Heart Ventricles, Active Transport, Cell Nucleus, A Kinase Anchor Proteins, Cardiomegaly, Models, Biological, Histone Deacetylases, Cell Line, Minor Histocompatibility Antigens, Phenylephrine, Chlorocebus aethiops, Animals, Guanine Nucleotide Exchange Factors, Humans, Myocytes, Cardiac, Molecular Biology, MEF2 Transcription Factors, Cell Biology, Cyclic AMP-Dependent Protein Kinases, 14-3-3 Proteins, Gene Expression Regulation, Myogenic Regulatory Factors, COS Cells
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