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

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

doi:10.1038/sj.emboj.7601502

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

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

Research output: Contribution to journal › Article › peer-review

95 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 Gα_s 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 language	English (US)
Pages (from-to)	53-64
Number of pages	12
Journal	EMBO Journal
Volume	26
Issue number	1
DOIs	https://doi.org/10.1038/sj.emboj.7601502
State	Published - Jan 10 2007
Externally published	Yes

Keywords

G proteins
GPCR
MAPK
Src

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.1038/sj.emboj.7601502

Cite this

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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.",

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AU - Sun, Yutong

AU - Huang, Jianyun

AU - Xiang, Yang

AU - Bastepe, Murat

AU - Jüppner, Harald

AU - Kobilka, Brian K.

AU - Zhang, J. Jillian

AU - Huang, Xin Yun

PY - 2007/1/10

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

Abstract

Keywords

ASJC Scopus subject areas

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