Alternative signaling: cardiomyocyte beta1-adrenergic receptors signal through EGFRs.

Acute stimulation of cardiac beta1-adrenergic receptors (beta1ARs) by norepinephrine represents the strongest endogenous mechanism for increasing cardiac function, but long-term stimulation induces cardiomyocyte apoptosis and contributes to cardiac disease. These effects have been attributed to coupling of the beta1AR to the stimulatory G protein (Gs) and classical cAMP-mediated signaling. In this issue of the JCI, Noma and colleagues report that cardiomyocyte beta1ARs may in addition deliver an antiapoptotic signal through transactivation of EGFRs (see the related article beginning on page 2445). Their findings provide a perspective for a novel class of receptor ligands that may direct beta1AR signaling toward alternative signaling pathways.