Beta-Adrenergic Receptors Cooperate With Transcription Factors: The "STAT" of Their Union.

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).