Control of Gαq signaling dynamics and GPCR cross-talk by GRKs. Academic Article uri icon

Overview

abstract

  • Numerous processes contribute to the regulation of G protein-coupled receptors (GPCRs), but relatively little is known about rapid mechanisms that control signaling on the seconds time scale or regulate cross-talk between receptors. Here, we reveal that the ability of some GPCR kinases (GRKs) to bind Gαq both drives acute signaling desensitization and regulates functional interactions between GPCRs. GRK2/3-mediated acute desensitization occurs within seconds, is rapidly reversible, and can occur upon local, subcellular activation. This rapid desensitization is kinase independent, insensitive to pharmacological inhibition, and generalizable across receptor families and effectors. We also find that the ability of GRK2 to bind G proteins also enables it to regulate the extent and timing of Gαq-dependent signaling cross-talk between GPCRs. Last, we find that G protein/GRK2 interactions enable a novel form of GPCR trafficking cross-talk. Together, this work reveals potent forms of Gαq-dependent GPCR regulation with wide-ranging pharmacological and physiological implications.

publication date

  • November 25, 2022

Identity

PubMed Central ID

  • PMC9699688

Scopus Document Identifier

  • 85142940611

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abq3363

PubMed ID

  • 36427324

Additional Document Info

volume

  • 8

issue

  • 47