Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR.
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.
Sun
Yutong
Y
Department of Physiology, Weill Medical College, Cornell University, New York, NY 10021, USA.
Huang
Jianyun
J
Xiang
Yang
Y
Bastepe
Murat
M
Jüppner
Harald
H
Kobilka
Brian K
BK
Zhang
J Jillian
JJ
Huang
Xin-Yun
XY
D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019204:GTP-Binding Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs