Novel beta2-adrenergic receptor signaling pathways

Abstract

The beta(2)-adrenergic receptor (beta(2)AR) is perhaps the most thoroughly investigated of all G-protein-coupled receptors. Although the classical pathway of beta(2)AR signaling involves agonist-promoted binding of the receptor to the heterotrimeric guanosine triphosphate-binding protein G(s), activation of adenylyl cyclase, and production of cyclic adenosine monophosphate (cAMP), current evidence suggests that beta(2)AR signaling is regulated by interaction with multiple proteins. These interactions fall into 3 major groups: guanosine triphosphate-binding proteins such as G(s) and G(i); protein kinases such as the cAMP-dependent protein kinase, protein kinase C, G-protein-coupled receptor kinases, and tyrosine kinases; and adaptor proteins such as arrestins, A-kinase anchoring proteins, and the Na(+)/H(+)-exchanger regulatory factor. This review discusses these various interactions with particular emphasis on their role in regulating beta(2)AR signaling and trafficking.