Role for β-arrestin in mediating paradoxical β2AR and PAR2 signaling in asthma.

Published

Journal Article (Review)

G protein-coupled receptors (GPCRs) utilize (at least) two signal transduction pathways to elicit cellular responses including the classic G protein-dependent, and the more recently discovered β-arrestin-dependent, signaling pathways. In human and murine models of asthma, agonist-activation of β2-adrenergic receptor (β2AR) or Protease-activated-receptor-2 (PAR2) results in relief from bronchospasm via airway smooth muscle relaxation. However, chronic activation of these receptors, leads to pro-inflammatory responses. One plausible explanation underlying the paradoxical effects of β2AR and PAR2 agonism in asthma is that the beneficial and harmful effects are associated with distinct signaling pathways. Specifically, G protein-dependent signaling mediates relaxation of airway smooth muscle, whereas β-arrestin-dependent signaling promotes inflammation. This review explores the evidence supporting the hypothesis that β-arrestin-dependent signaling downstream of β2AR and PAR2 is detrimental in asthma and examines the therapeutic opportunities for selectively targeting this pathway.

Full Text

Duke Authors

Cited Authors

  • Walker, JKL; DeFea, KA

Published Date

  • June 5, 2014

Published In

Volume / Issue

  • 16 /

Start / End Page

  • 142 - 147

PubMed ID

  • 24907413

Pubmed Central ID

  • 24907413

Electronic International Standard Serial Number (EISSN)

  • 1471-4973

International Standard Serial Number (ISSN)

  • 1471-4892

Digital Object Identifier (DOI)

  • 10.1016/j.coph.2014.03.007

Language

  • eng