Beyond G protein and arrestin: GRK2-biased β₂AR signaling

Trends Pharmacol Sci. 2025 Oct;46(10):928-930. doi: 10.1016/j.tips.2025.07.010. Epub 2025 Aug 1.

Abstract

Biased G-protein-coupled receptor (GPCR) signaling is reshaping drug discovery by enabling pathway-selective drug action. Recent work by Motso et al. identified GPCR kinase 2 (GRK2) as a non-canonical transducer, independent of G proteins or β-arrestins, redefining the biased signaling landscape and highlighting GRK2 as a novel therapeutic target for selective modulation of GPCR-driven metabolic responses.

Keywords: biased agonism; diabetes; precision pharmacology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • G-Protein-Coupled Receptor Kinase 2* / metabolism
  • GTP-Binding Proteins / metabolism
  • Humans
  • Receptors, Adrenergic, beta-2* / metabolism
  • Signal Transduction / drug effects

Substances

  • G-Protein-Coupled Receptor Kinase 2
  • GRK2 protein, human
  • GTP-Binding Proteins
  • Receptors, Adrenergic, beta-2