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 journalArticle

82 Citations (Scopus)

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

Fingerprint

G-Protein-Coupled Receptors
GTP-Binding Proteins
Switches
Adrenergic Receptors
Heterotrimeric GTP-Binding Proteins
Adrenergic Agonists
src-Family Kinases
Fibroblasts
Mitogen-Activated Protein Kinases
Protein-Tyrosine Kinases
Cells

Keywords

  • G proteins
  • GPCR
  • MAPK
  • Src

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Sun, Y., Huang, J., Xiang, Y. K., Bastepe, M., Jüppner, H., Kobilka, B. K., ... Huang, X. Y. (2007). Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR. EMBO Journal, 26(1), 53-64. https://doi.org/10.1038/sj.emboj.7601502

Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR. / Sun, Yutong; Huang, Jianyun; Xiang, Yang Kevin; Bastepe, Murat; Jüppner, Harald; Kobilka, Brian K.; Zhang, J. Jillian; Huang, Xin Yun.

In: EMBO Journal, Vol. 26, No. 1, 10.01.2007, p. 53-64.

Research output: Contribution to journalArticle

Sun, Y, Huang, J, Xiang, YK, Bastepe, M, Jüppner, H, Kobilka, BK, Zhang, JJ & Huang, XY 2007, 'Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR', EMBO Journal, vol. 26, no. 1, pp. 53-64. https://doi.org/10.1038/sj.emboj.7601502
Sun, Yutong ; Huang, Jianyun ; Xiang, Yang Kevin ; Bastepe, Murat ; Jüppner, Harald ; Kobilka, Brian K. ; Zhang, J. Jillian ; Huang, Xin Yun. / Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR. In: EMBO Journal. 2007 ; Vol. 26, No. 1. pp. 53-64.
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