cAMP-binding protein Epac induces cardiomyocyte hypertrophy

被引：165

作者：

Morel, E ^{[1
]}

Marcantoni, A ^{[1
]}

Gastineau, M ^{[1
]}

Birkedal, R ^{[1
]}

Rochais, F ^{[1
]}

Garnier, A ^{[1
]}

Lompré, AM ^{[1
]}

Vandecasteele, G ^{[1
]}

Lezoualc'h, F ^{[1
]}

机构：

[1] Univ Paris 11, Fac Pharm, Inserm U446, IFR 75, F-92296 Chatenay Malabry, France

来源：

CIRCULATION RESEARCH | 2005年 / 97卷 / 12期

关键词：

cAMP; guanine nucleotide exchange factor; small G protein; transcription factor;

D O I：

10.1161/01.RES.0000194325.31359.86

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

cAMP is one of the most important second messenger in the heart. The discovery of Epac as a guanine exchange factor (GEF), which is directly activated by cAMP, raises the question of the role of this protein in cardiac cells. Here we show that Epac activation leads to morphological changes and induces expression of cardiac hypertrophic markers. This process is associated with a Ca2+-dependent activation of the small GTPase, Rac. In addition, we found that Epac activates a prohypertrophic signaling pathway, which involves the Ca2+ sensitive phosphatase, calcineurin, and its primary downstream effector, NFAT. Rac is involved in Epac-induced NFAT dependent cardiomyocyte hypertrophy. Blockade of either calcineurin or Rac activity blunts the hypertrophic response elicited by Epac indicating these signaling molecules coordinately regulate cardiac gene expression and cellular growth. Our results thus open new insights into the signaling pathways by which cAMP may mediate its biological effects and identify Epac as a new positive regulator of cardiac growth.

引用

页码：1296 / 1304

页数：9

共 46 条

[1] Dilated cardiomyopathy and sudden death resulting from constitutive activation of protein kinase A [J].