Update on current concepts of the molecular basis of beta2-adrenergic receptor signaling.
The proposed manner by which beta(2)-adrenergic receptors signal has dramatically changed from earlier concepts that centered on a lock-and-key mechanism in which the receptor acts as a simple switch. We now know that beta(2)-adrenergic receptors spontaneously toggle to an activated state (R*) and that the equilibrium between R (the inactive state) and R* can be altered by ligands. In addition, the R* conformation is likely to consist of multiple subspecies that may favor certain signaling pathways or regulatory events. Changes in agonist structure alter the abundance of certain subspecies of R*. Indeed, multifunctional coupling is common with many G-protein-coupled receptors and can be modulated pharmacologically to attain specific outcomes. In addition to providing the basis for development of new beta-agonists for unique signaling, these properties can be extended such that beta(2)-adrenergic receptors, or highly modified "designer" receptors, can be used for gene therapy with highly specific effects.
Liggett
Stephen B
SB
Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
D000595:Amino Acid Sequence; D015316:Genetic Therapy; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D018343:Receptors, Adrenergic, beta-2; D011956:Receptors, Cell Surface