Beta-arrestin-biased ligands at seven-transmembrane receptors.

Journal Article (Journal Article;Review)

Seven-transmembrane receptors (7TMRs), the most common molecular targets of modern drug therapy, are critically regulated by beta-arrestins, which both inhibit classic G-protein signaling and initiate distinct beta-arrestin signaling. The interplay of G-protein and beta-arrestin signals largely determines the cellular consequences of 7TMR-targeted drugs. Until recently, a drug's efficacy for beta-arrestin recruitment was believed to be proportional to its efficacy for G-protein activities. This paradigm restricts 7TMR drug effects to a linear spectrum of responses, ranging from inhibition of all responses to stimulation of all responses. However, it is now clear that 'biased ligands' can selectively activate G-protein or beta-arrestin functions and thus elicit novel biological effects from even well-studied 7TMRs. Here, we discuss the current state of beta-arrestin-biased ligand research and the prospects for beta-arrestin bias as a therapeutic target. Consideration of ligand bias might have profound influences on the way scientists approach 7TMR-targeted drug discovery.

Full Text

Duke Authors

Cited Authors

  • Violin, JD; Lefkowitz, RJ

Published Date

  • August 2007

Published In

Volume / Issue

  • 28 / 8

Start / End Page

  • 416 - 422

PubMed ID

  • 17644195

International Standard Serial Number (ISSN)

  • 0165-6147

Digital Object Identifier (DOI)

  • 10.1016/


  • eng

Conference Location

  • England