GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure
INSERM UMR-1048, Institute of Metabolic and Cardiovascular Diseases, Université de Toulouse III—Paul Sabatier, 31432 Toulouse, France
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Cells 2021, 10(1), 154; https://doi.org/10.3390/cells10010154
Received: 26 November 2020 / Revised: 6 January 2021 / Accepted: 8 January 2021 / Published: 14 January 2021
(This article belongs to the Special Issue Novel Insights on G Protein-Coupled Receptor Kinases: From Cell Biology to Pathology)
β-adrenergic receptors (β-ARs) play a major role in the physiological regulation of cardiac function through signaling routes tightly controlled by G protein-coupled receptor kinases (GRKs). Although the acute stimulation of β-ARs and the subsequent production of cyclic AMP (cAMP) have beneficial effects on cardiac function, chronic stimulation of β-ARs as observed under sympathetic overdrive promotes the development of pathological cardiac remodeling and heart failure (HF), a leading cause of mortality worldwide. This is accompanied by an alteration in cAMP compartmentalization and the activation of the exchange protein directly activated by cAMP 1 (Epac1) signaling. Among downstream signals of β-ARs, compelling evidence indicates that GRK2, GRK5, and Epac1 represent attractive therapeutic targets for cardiac disease. Here, we summarize the pathophysiological roles of GRK2, GRK5, and Epac1 in the heart. We focus on their signalosome and describe how under pathological settings, these proteins can cross-talk and are part of scaffolded nodal signaling systems that contribute to a decreased cardiac function and HF development.
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MDPI and ACS Style
Laudette, M.; Formoso, K.; Lezoualc’h, F. GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure. Cells 2021, 10, 154. https://doi.org/10.3390/cells10010154
AMA Style
Laudette M, Formoso K, Lezoualc’h F. GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure. Cells. 2021; 10(1):154. https://doi.org/10.3390/cells10010154
Chicago/Turabian StyleLaudette, Marion; Formoso, Karina; Lezoualc’h, Frank. 2021. "GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure" Cells 10, no. 1: 154. https://doi.org/10.3390/cells10010154
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