Key result
Modified peptide SII acts as a biased AT1R agonist, activating beta-arrestin without G protein coupling.
Why the study?
GPCRs including the angiotensin II type 1 receptor can be modulated by biased agonists that selectively activate specific intracellular signaling pathways, but the role of biased AT1R signaling requires summarization.
This review highlights the molecular mechanisms of biased agonism at the angiotensin II type 1 receptor, which may inform the development of more selective cardiovascular therapeutics.
May guide biased AT1R ligand development; leaves open clinical translation and outcomes in cardiovascular disease.
G protein-coupled receptors (GPCRs) can be activated by multiple ligands and exhibit the capacity to couple to numerous intracellular signal transduction pathways. This property allows GPCRs to be modulated by biased agonists that selectively activate specific subsets of GPCR-regulated cellular signaling proteins. The angiotensin II type 1 receptor (AT1R) is a GPCR that endogenously binds to the peptide ligand angiotensin II. More recently it has been demonstrated that a modified peptide, [Sar1I-le4-Ile8]-angiotensin II (SII) acts as a biased agonist towards the AT1R. SII binds to the AT1R without promoting heterotrimeric G protein-coupling, but serves to link the receptor to the beta-arrestin-dependent activation of the mitogen activated protein kinase pathway. The present mini-review summarizes current knowledge regarding the role of biased agonists in stimulating biased AT1R signaling.
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Godin et al. (2012) reported a review. [Sar1I-le4-Ile8]-angiotensin II (SII) was evaluated. The modified peptide [Sar1I-le4-Ile8]-angiotensin II (SII) acts as a biased agonist towards the AT1R, linking the receptor to beta-arrestin-dependent activation without G protein-coupling.
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