Cellular expression of the carboxyl terminus of a G protein-coupled receptor kinase attenuates G beta gamma-mediated signaling.
Open accessAbstract
The beta gamma subunits (G beta gamma) of heterotrimeric G proteins modulate the activity of several signal-transducing effector molecules including G protein-coupled receptor kinases. G beta gamma binds to the carboxyl terminus of the beta-adrenergic receptor kinase (beta ARK) and regulates its activity. To investigate the effect of such a G beta gamma-binding domain on heterologous G beta gamma interactions, various receptors that can stimulate phospholipase C and/or type II adenylate cyclase were coexpressed in COS-7 cells with the carboxyl terminus of beta ARK1. Phosphoinositol hydrolysis in response to activation of receptors that stimulate phospholipase C via Gi beta gamma (alpha 2-adrenergic and M2-muscarinic cholinergic receptors) was markedly inhibited by the coexpressed beta ARK1 polypeptide, whereas that mediated by Gq alpha subunits (alpha 1-adrenergic and M1-muscarinic cholinergic receptors) was unaffected. Increased cellular cAMP levels due to stimulation of receptors and coexpressed adenylate cyclase II displayed marked inhibition in the presence of the beta ARK1 polypeptide. Moreover, inhibition of adenylate cyclase produced by alpha 2-adrenergic receptor stimulation (a Gi alpha-mediated process) was unaffected, indicating that the beta ARK1 polypeptide provides a useful tool for distinguishing between G alpha and G beta gamma pathways.
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Coexpression of bARKct restored GEF-H1-eGFP localization to the microtubules.
“To demonstrate the specificity of the Gbg effect on GEF-H1 redistribution, we co-expressed the Gbg-specific antagonist peptide, bARKct, derived from the Gbg-binding domain of b-adrenergic receptor kinase 1, which specifically inhibits Gbg-dependent signalling 16 , and noted that coexpression of bARKct restored GEF-H1-eGFP localization to the microtubules (Fig. 2c; Supplementary Fig. 2a).”
From Mechanistic insight into GPCR-mediated activation of the microtubule-associated RhoA exchange factor GEF-H1 (2014) · cites this paper as [16]
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Hormonal stimulation of adenylyl cyclase through Gi-protein βγ subunits
Federman, A. D., Conklin, B. R., Schrader, K. A., Reed, R. R., & Bourne, H. R. (1992) · Nature · doi:10.1038/356159a0 · Cited by 624 · see citing works
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- Authors
- Koch, W. J., Hawes, B. E., Inglese, J., Luttrell, L. M., & Lefkowitz, R. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-02
- Volume
- 269
- Issue
- 8
- Pages
- 6193-6197
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2160146943
- Cited by
- 421
- References
- 2
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 9 · 2015: 4 · 2014: 8 · 2013: 11 · 2012: 6
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 16037)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- beta-adrenergic receptor kinase, heterotrimeric G proteins, phosphoinositide hydrolysis, phospholipase C, cyclic AMP, alpha2-adrenoceptors, muscarinic receptors, Gi alpha, Gαq
- MeSH terms
- Adenylyl Cyclases, Animals, Base Sequence, Cattle, Cell Line, Enzyme Activation, Molecular Sequence Data, Oligodeoxyribonucleotides, Peptide Fragments, Type C Phospholipases, Signal Transduction, Cyclic AMP-Dependent Protein Kinases, GTP-Binding Proteins, beta-Adrenergic Receptor Kinases, Cyclic AMP-Dependent Protein Kinase Type II
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