Imperial College London
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DrBenJones

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Senior Lecturer in Metabolic Medicine
 
 
 
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Contact

 

ben.jones

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fang:2020:10.1021/acsptsci.0c00022,
author = {Fang, Z and Chen, S and Pickford, P and Broichhagen, J and Hodson, DJ and Corrêa, IR and Kumar, S and Görlitz, F and Dunsby, C and French, PMW and Rutter, GA and Tan, T and Bloom, SR and Tomas, A and Jones, B},
doi = {10.1021/acsptsci.0c00022},
journal = {ACS Pharmacology & Translational Science},
pages = {345--360},
title = {The influence of peptide context on signaling and trafficking of glucagon-like peptide-1 receptor biased agonists},
url = {http://dx.doi.org/10.1021/acsptsci.0c00022},
volume = {3},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Signal bias and membrane trafficking have recently emerged as important considerations in the therapeutic targeting of the glucagon-like peptide-1 receptor (GLP-1R) in type 2 diabetes and obesity. In the present study, we have evaluated a peptide series with varying sequence homology between native GLP-1 and exendin-4, the archetypal ligands on which approved GLP-1R agonists are based. We find notable differences in agonist-mediated cyclic AMP signaling, recruitment of β-arrestins, endocytosis, and recycling, dependent both on the introduction of a His → Phe switch at position 1 and the specific midpeptide helical regions and C-termini of the two agonists. These observations were linked to insulin secretion in a beta cell model and provide insights into how ligand factors influence GLP-1R function at the cellular level.
AU  - Fang,Z
AU  - Chen,S
AU  - Pickford,P
AU  - Broichhagen,J
AU  - Hodson,DJ
AU  - Corrêa,IR
AU  - Kumar,S
AU  - Görlitz,F
AU  - Dunsby,C
AU  - French,PMW
AU  - Rutter,GA
AU  - Tan,T
AU  - Bloom,SR
AU  - Tomas,A
AU  - Jones,B
DO  - 10.1021/acsptsci.0c00022
EP  - 360
PY  - 2020///
SN  - 2575-9108
SP  - 345
TI  - The influence of peptide context on signaling and trafficking of glucagon-like peptide-1 receptor biased agonists
T2  - ACS Pharmacology & Translational Science
UR  - http://dx.doi.org/10.1021/acsptsci.0c00022
UR  - https://pubs.acs.org/doi/10.1021/acsptsci.0c00022
UR  - http://hdl.handle.net/10044/1/77863
VL  - 3
ER  -
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