Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor

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Wootten, Denise; Reynolds, Christopher A.; Smith, Kevin J.; Mobarec, Juan C.; Furness, Sebastian G.B.; Miller, Laurence J.; Christopoulos, Arthur; Sexton, Patrick M.;
  • Publisher: Elsevier BV
  • Journal: Biochemical Pharmacology, volume 118, pages 68-87 (issn: 0006-2952, eissn: 1873-2968)
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  • Identifiers: pmc: PMC5063953, doi: 10.1016/j.bcp.2016.08.015
  • Subject: GLP-1, glucagon-like peptide-1 | CHO, Chinese hamster ovary | GCGR, glucagon receptor | cAMP, 3′,5′-cyclic adenosine monophosphate | iCa2+, intracellular calcium | Biased agonism | Article | TM, transmembrane helix | DMEM, Dulbecco’s modified Eagle medium | GPCR, G protein-coupled receptor | Glucagon-like peptide-1 receptor | Cell signaling | Biochemistry | Pharmacology | pERK, extracellular signal-regulated kinase 1 and 2 phosphorylation | PBS, phosphate buffered saline | FBS, fetal bovine serum | CRF1R, corticotrophin releasing factor receptor-1 | G protein-coupled receptor

Class B GPCRs can activate multiple signalling effectors with the potential to exhibit biased agonism in response to ligand stimulation. Previously, we highlighted key TM domain polar amino acids that were crucial for the function of the GLP-1 receptor, a key therapeuti... View more