AKAP-Lbc Mobilizes a Cardiac Hypertrophy Signaling Pathway

被引：116

作者：

Carnegie, Graeme K. ^{[1
,5
]}

Soughayer, Joseph ^{[1
,5
]}

Smith, F. Donelson ^{[1
,5
]}

Pedroja, Benjamin S. ^{[1
,5
]}

Zhang, Fang ^{[1
,5
]}

Diviani, Dario ^{[2
]}

Bristow, Michael R. ^{[3
]}

Kunkel, Maya T. ^{[4
]}

Newton, Alexandra C. ^{[4
]}

Langeberg, Lorene K. ^{[1
,5
]}

Scott, John D. ^{[1
,5
]}

机构：

[1] Univ Washington, Howard Hughes Med Inst, Dept Pharmacol, Sch Med, Seattle, WA 98195 USA

[2] Univ Lausanne, Dept Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland

[3] Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80262 USA

[4] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[5] Oregon Hlth & Sci Univ, Vollum Inst, Howard Hughes Med Inst, Portland, OR 97239 USA

来源：

MOLECULAR CELL | 2008年 / 32卷 / 02期

关键词：

D O I：

10.1016/j.molcel.2008.08.030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：169 / 179

页数：11

共 44 条

[1] The A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates α1 adrenergic receptor-induced cardiomyocyte hypertrophy [J].