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, beta(2)-adrenergic receptors (beta(2)-ARs) signal through Galpha(s) to activate the mitogen-activated protein kinase pathway in mouse embryonic fibroblast cells. At high agonist concentrations, signals are also transduced through beta(2)-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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Animals
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Cricetinae
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Fibroblasts / metabolism
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GTP-Binding Protein alpha Subunits, Gs / metabolism
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GTP-Binding Protein alpha Subunits, Gs / physiology*
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GTP-Binding Proteins / metabolism*
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Humans
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Mice
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Molecular Sequence Data
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Phosphorylation
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Receptors, Adrenergic, beta-2 / metabolism*
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Receptors, G-Protein-Coupled / metabolism*
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Signal Transduction
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src-Family Kinases / metabolism
Substances
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Receptors, Adrenergic, beta-2
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Receptors, G-Protein-Coupled
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src-Family Kinases
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Extracellular Signal-Regulated MAP Kinases
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GTP-Binding Proteins
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GTP-Binding Protein alpha Subunits, Gs