Epac1 inhibition as a novel cardioprotective strategy: lights and shadows on GRK5 canonical and non-canonical functions

β1-adrenergic receptors (β1AR) are members of the super-family of G protein-coupled receptors (GPCR) and major regulators of cardiac function. β1AR stimulation leads to G protein-mediated generation of the second messenger cyclic adenosine monophosphate (cAMP) and activation of effectors such as cAMP-dependent Protein Kinase A (PKA) or Exchange Proteins Activated by cAMP (Epac) (Figure 1). In addition, β1AR stimulation activates GPCR kinases (GRK) ‘canonical’ pathways,1 regulating β1AR phosphorylation, desensitization, down-regulation, degradation and recycling as well as activation of β-arrestin-dependent, G protein-independent signalling (Figure 1).2 GRK5 non-canonical activities in the nucleus have been also recently demonstrated, and new complexes/interactions between GRK5 and other proteins are being continuously identified.2
Source: Cardiovascular Research - Category: Cardiology Source Type: research