Gβ 4 γ 1 as a modulator of M3 muscarinic receptor signalling and novel roles of Gβ 1 subunits in the modulation of cellular signalling
Copyright policy )Gβ 4 γ 1 as a modulator of M3 muscarinic receptor signalling and novel roles of Gβ 1 subunits in the modulation of cellular signalling
Much is known about the how Gβγ subunits regulate effectors in response to G protein-coupled receptor stimulation. However, there is still a lot we don't know about how specific combinations of Gβ and Gγ are wired into different signalling pathways. Here, using an siRNA screen for different Gβ and Gγ subunits, we examined an endogenous M3 muscarinic receptor signalling pathway in HEK 293 cells. We observed that Gβ(4) subunits were critical for calcium signalling and a downstream surrogate measured as ERK1/2 MAP kinase activity. A number of Gγ subunits could partner with Gβ(4) but the best coupling was seen via Gβ(4)γ(1). Intriguingly, knocking down Gβ(1) actually increased signalling through the M3-mAChR most likely via an increase in Gβ(4) levels. We noted that Gβ(1) occupies the promoter of Gβ(4) and may participate in maturation of its mRNA. This highlights a new role for Gβγ signalling beyond their canonical roles in cellular signalling.
- McGill University Canada
- University of Toronto Canada
- University of Queensland Australia
- University of Queensland Australia
- Integrated DNA Technologies (United States) United States
570, Beta-Gamma-Subunits, MAP Kinase Signaling System, Gene-Expression, Cholinergic Agonists, Messenger-Rna, Hnrnp Particles, Oxytocin Receptor, GTP-Binding Protein gamma Subunits, Humans, Calcium Signaling, RNA, Messenger, Beta(2)-Adrenergic Receptor, Promoter Regions, Genetic, Mitogen-Activated Protein Kinase 1, Receptor, Muscarinic M3, Heterotrimeric G-Protein, Glucocorticoid-Receptor, Binding Sites, Mitogen-Activated Protein Kinase 3, Dose-Response Relationship, Drug, GTP-Binding Protein beta Subunits, Receptors, Muscarinic, HEK293 Cells, Gene Expression Regulation, Transcriptional Activity, Carbachol, RNA Interference, Protein Multimerization, Erk1/2 Activation, Signal Transduction
570, Beta-Gamma-Subunits, MAP Kinase Signaling System, Gene-Expression, Cholinergic Agonists, Messenger-Rna, Hnrnp Particles, Oxytocin Receptor, GTP-Binding Protein gamma Subunits, Humans, Calcium Signaling, RNA, Messenger, Beta(2)-Adrenergic Receptor, Promoter Regions, Genetic, Mitogen-Activated Protein Kinase 1, Receptor, Muscarinic M3, Heterotrimeric G-Protein, Glucocorticoid-Receptor, Binding Sites, Mitogen-Activated Protein Kinase 3, Dose-Response Relationship, Drug, GTP-Binding Protein beta Subunits, Receptors, Muscarinic, HEK293 Cells, Gene Expression Regulation, Transcriptional Activity, Carbachol, RNA Interference, Protein Multimerization, Erk1/2 Activation, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).19 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!