Details
- Autor(en) / Beteiligte
- Titel
- AKAP-Lbc Mobilizes a Cardiac Hypertrophy Signaling Pathway
- Ist Teil von
- Molecular cell, 2008-10, Vol.32 (2), p.169-179
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2008
- Link zum Volltext
- Quelle
- EZB Electronic Journals Library
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2008.08.030Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3169907
- Format
- –
- Schlagworte
- 14-3-3 Proteins - metabolism, A Kinase Anchor Proteins - genetics, A Kinase Anchor Proteins - metabolism, A Kinase Anchor Proteins - physiology, Active Transport, Cell Nucleus, Animals, Cardiomegaly - metabolism, Cell Line, Cercopithecus aethiops, COS Cells, Cyclic AMP-Dependent Protein Kinases - metabolism, Gene Expression Regulation, Guanine Nucleotide Exchange Factors - genetics, Guanine Nucleotide Exchange Factors - metabolism, Guanine Nucleotide Exchange Factors - physiology, Heart Ventricles - drug effects, Histone Deacetylases - metabolism, Humans, HUMDISEASE, MEF2 Transcription Factors, Minor Histocompatibility Antigens, Models, Biological, Myocytes, Cardiac - drug effects, Myocytes, Cardiac - metabolism, Myocytes, Cardiac - pathology, Myogenic Regulatory Factors - metabolism, Phenylephrine - pharmacology, Phosphorylation, Protein Kinase C - metabolism, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - metabolism, Proto-Oncogene Proteins - physiology, Rats, RNA Interference, Signal Transduction, SIGNALING