Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR

Yutong Sun, Jianyun Huang, Yang Kevin Xiang, Murat Bastepe, Harald Jüppner, Brian K. Kobilka, J. Jillian Zhang, Xin Yun Huang

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

G-protein-coupled receptors (GPCRs) mostly signal through heterotrimeric G proteins. Increasing evidence suggests that GPCRs could function in a G-protein-independent manner. Here, we show that at low concentrations of an agonist, β2-adrenergic receptors (β2-ARs) signal through Gαs to activate the mitogen-activated protein kinase pathway in mouse embryonic fibroblast cells. At high agonist concentrations, signals are also transduced through β2-ARs via an additional pathway that is G-protein-independent but tyrosine kinase Src-dependent. This new dosage-dependent switch of signaling modes of GPCRs has significant implications for GPCR intrinsic properties and desensitization.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalEMBO Journal
Volume26
Issue number1
DOIs
StatePublished - Jan 10 2007
Externally publishedYes

Keywords

  • G proteins
  • GPCR
  • MAPK
  • Src

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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