ArticleThe Journal of biological chemistry2011
Helix 8 plays a crucial role in bradykinin B(2) receptor trafficking and signaling.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- A novel brachydactyly type E syndrome caused by variants in helix 8 of the PTH1R.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Insights on the G protein-coupled receptor helix 8 solution structure and orientation using a neurotensin receptor 1 peptide.Protein science : a publication of the Protein Society · 2024Article
- Function and structure of bradykinin receptor 2 for drug discovery.Acta pharmacologica Sinica · 2023Review
- Direct addition of poly-lysine or poly-ethylenimine to the medium: A simple alternative to plate pre-coating.PloS one · 2022Article
- Identification of Key Regions Mediating Human Melatonin Type 1 Receptor Functional Selectivity Revealed by Natural Variants.ACS pharmacology & translational science · 2021Article
- Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Role of the Helix-8 and C-Terminal Tail in Regulating Proteinase Activated Receptor 2 Signaling.ACS pharmacology & translational science · 2020Article
- Conformational dynamics of a G protein-coupled receptor helix 8 in lipid membranes.Science advances · 2020Article
- Loss-of-function of Endothelin receptor type A results in Oro-Oto-Cardiac syndrome.American journal of medical genetics. Part A · 2020Article
- Chemokines and galectins form heterodimers to modulate inflammation.EMBO reports · 2020Article
- Protein Interactors and Trafficking Pathways That Regulate the Cannabinoid Type 1 Receptor (CB1R).Frontiers in molecular neuroscience · 2020Review
- Role of Helix 8 in Dopamine Receptor Signaling.Biomolecules & therapeutics · 2019Article
- In vivo assembly and large-scale purification of a GPCR - Gα fusion with Gβγ, and characterization of the active complex.PloS one · 2019Article
- The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains.mBio · 2018Article
- G protein-coupled receptors directly bind filamin A with high affinity and promote filamin phosphorylation.Biochemistry · 2015Article
- Helix 8 and the i3 loop of the muscarinic M3 receptor are crucial sites for its regulation by the Gβ5-RGS7 complex.Biochemistry · 2015Article
- Proline substitutions in a Mip-like peptidyl-prolylBiochimie open · 2015Article
- Kinin-stimulated B1 receptor signaling depends on receptor endocytosis whereas B2 receptor signaling does not.Neurochemical research · 2014Article
- Novel screening assay for the selective detection of G-protein-coupled receptor heteromer signaling.The Journal of pharmacology and experimental therapeutics · 2013Article
- Binding characteristics of [3H]-JSM10292: a new cell membrane-permeant non-peptide bradykinin B2 receptor antagonist.British journal of pharmacology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon activation the human bradykinin B(2) receptor (B(2)R) acts as guanine nucleotide exchange factor for the G proteins G(q/11) and G(i). Thereafter, it gets phosphorylated by G protein-coupled receptor kinases (GRKs) and recruits β-arrestins, which block further G protein activation and promote B(2)R internalization via clathrin-coated pits. As for most G protein-coupled receptors of family A, an intracellular helix 8 after transmembrane domain 7 is also predicted for the B(2)R. We show here that disruption of helix 8 in the B(2)R by either C-terminal truncation or just by mutation of a central amino acid (Lys-315) to a helix-breaking proline resulted in strong reduction of surface expression. Interestingly, this malfunction could be overcome by the addition of the membrane-permeable B(2)R antagonist JSM10292, suggesting that helix 8 has a general role for conformational stabilization that can be accounted for by an appropriate antagonist. Intriguingly, an intact helix 8, but not the C terminus with its phosphorylation sites, was indispensable for receptor sequestration and for interaction of the B(2)R with GRK2/3 and β-arrestin2 as shown by co-immunoprecipitation. Recruitment of β-arrestin1, however, required the presence of the C terminus. Taken together, our results demonstrate that helix 8 of the B(2)R plays a crucial role not only in efficient trafficking to the plasma membrane or the activation of G proteins but also for the interaction of the B(2)R with GRK2/3 and β-arrestins. Additional data obtained with chimera of B(2)R with other G protein-coupled receptors of family A suggest that helix 8 might have similar functions in other GPCRs as well.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.