title: New perspectives in cAMP-signaling modulation.
abstract: Cyclic adenosine 3',5'-monophosphate (cAMP) mediates the biological effects of various hormones and neurotransmitters. Stimulation of cardiac β-adrenergic receptors (β-AR) via catecholamines leads to activation of adenylyl cyclases and increases cAMP production to enhance myocardial function. Because many other receptors signaling through cAMP generation exist in cardiac myocytes, a central question is how different hormones induce distinct cellular responses through the same second messenger. A large body of evidence suggests that the localization and compartmentalization of β-AR/cAMP signaling affects the net outcome of biological functions. Spatiotemporal dynamics of cAMP action is achieved by various proteins, including protein kinase A (PKA), phosphodiesterases, and scaffolding proteins such as A-kinase-anchoring proteins. In addition, the discovery of the cAMP target Epac (exchange proteins directly activated by cAMP), which functions in a PKA-independent manner, represents a novel mechanism for governing cAMP-signaling specificity. Aberrant cAMP signaling through dysregulation of β-AR/cAMP compartmentalization may contribute to cardiac remodeling and heart failure.
authors: INSERM, UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, 1 Avenue Jean Poulhès, BP 84225, 31342, Toulouse Cedex 4, France.
authors: Magali
authors: M
authors: Berthouze
authors: Anne-Coline
authors: AC
authors: Laurent
authors: Magali
authors: M
authors: Breckler
authors: Frank
authors: F
authors: Lezoualc'h
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