Making the switch: The role of Gq in driving GRK selectivity at GPCRs

Selective engagement of signal transducers such as G proteins and β-arrestins with GPCRs upon stimulation with biased agonists is thought to be due to distinct receptor conformations. Kawakami et al. propose an additional mechanism whereby activation of Gq determines GPCR kinase subtype selectivity to the activated angiotensin receptor, leading to distinct binding modalities of β-arrestins and functional outcomes.