Key result
Beta-adrenergic receptors regulate cardiovascular function through classical cAMP/PKA pathways, beta-arrestin-dependent ERK activation, and trans-activation of receptor tyrosine kinases.
Beta-adrenergic receptors regulate cardiovascular function and remodeling through both classical cAMP/PKA pathways and alternative signaling involving ERK and receptor tyrosine kinase trans-activation.
Highlights dual beta-adrenergic signaling; leaves open whether ERK/RTK pathways enable selective therapies beyond current beta-blockers.
Through their wide tissue/cellular distribution, beta-adrenoreceptors (BAR) are key regulators of cardiovascular function and remodeling. Classically, B1-2ARs positively influence all aspects of cardiac contractility through G-alpha-s coupling to adenylyl cyclase and cyclic Adenosine Monophosphate (cAMP)/Protein Kinase A (PKA) phosphorylation of critical effectors of excitation-contraction (EC) coupling(1), whereas B3AR exert antipathetic effects, thereby attenuating those of B1-2AR stimulation(2, 3). B1-2ARs are also known to initiate signaling that is independent of PKA/cAMP and involves beta-arrestin-dependent activation of Extracellular signal-Regulated Kinases (ERK). Moreover, as many G-protein coupled receptors (GPCRs), B1-2AR can trans-activate Receptor Tyrosine Kinases (RTKs), e.g. Epidermal Growth Factor Receptor (EGFR), thereby producing wider effects on cellular growth and survival(4).
No takes yet. Share an insight, caveat, or question.
Jean‐Luc Balligand (2015) conducted a review in Cardiovascular function and remodeling. Beta-adrenergic receptors was evaluated. Beta-adrenergic receptors regulate cardiovascular function through classical cAMP/PKA pathways, beta-arrestin-dependent ERK activation, and trans-activation of receptor tyrosine kinases.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: