The glucagon-like peptide 1 receptor (GLP-1R) can be activated by a number of endogenous peptide hormones, including extended, processed, glycine extended and carboxy-terminally amidated versions of glucagon-like peptide 1 (GLP-1). While the main focus of the literature has been on the processed, amidated form, GLP-1(7-36) NH2, the other forms of this peptide are likely to be secreted in physiologically relevant amounts under certain circumstances. This study builds on our existing work examining the effect of mutation of conserved trans membrane polar residues within the receptor to understand the nature of binding and pleiotropic signaling in response to these alternatively processed versions of this important incretin hormone. We show that extended and processed peptides differ not only in their binding to the receptor but also in the way the receptor is engaged for activation that leads to differential signaling bias exhibited by these peptides.
[1]Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, 381 Royal Parade, Parkville, Vic 3052, Australia;
[2]Monash Univ, Dept Pharmacol, Parkville, Vic, Australia;
[3]Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
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