mProX™ Human BRS3 Stable Cell Line

Guo M, et al. "Dynamic Phosphoproteomics of BRS3 Activation Reveals the Hippo Signaling Pathway ." Journal of proteome research, 2023.
In this study, the authors use a quantitative phosphoproteomics approach to investigate the signal transductions involved in the activation of Bombesin receptor subtype-3 (BRS3), an orphan G-protein coupled receptor (GPCR). The lung cancer cell line H1299-BRS3 was treated with the BRS3 agonist MK-5046 for different durations, and phosphopeptides were enriched and analyzed using immobilized titanium (IV) ion affinity chromatography (Ti(4+)-IMAC) and label-free quantification (LFQ) analysis. A total of 11,938 phosphopeptides were identified, corresponding to 3,430 phosphoproteins and 10,820 phosphosites. The results reveal that BRS3 activation significantly regulates the Hippo signaling pathway, and verification experiments show that this downregulation can induce dephosphorylation and nucleus localization of Yes-associated protein (YAP) and promote cell migration. These findings suggest that BRS3 activation may contribute to cell migration through regulation of the Hippo signaling pathway.
Pubmed: 37368948   DOI: 10.1021/acs.jproteome.3c00116

Wu L, et al. "Discovery of Dimethyl Shikonin Oxime 5a, a Potent, Selective Bombesin Receptor ." Journal of medicinal chemistry, 2023.
The orphan G(alphaq) protein-coupled receptor, bombesin receptor subtype-3 (BB(3), BRS-3), has been the subject of research to understand its various physiological functions. The use of novel synthetic ligands for BB(3) has emerged as an alternative and appealing method for this purpose. In this context, the findings of a study revealed the strong affinity of DMAKO-00 and its derivatives with BB(3). Among them, dimethyl shikonin oxime 5a (DSO-5a) was identified as the most potent agonist (pEC(50) = 8.422 in IP-1 accumulation) which was 898-fold more active than DMAKO-00. The study also demonstrated the positive effects of DSO-5a, a compound of DMAKO-00 derivatives, in improving glucose tolerance and homeostasis in mice through BB(3) without affecting brain function. The study further revealed that DSO-5a achieves this through the upregulation of PPAR-gamma activity via BB(3), as shown by a quantitative proteomics approach. These findings suggest that DSO-5a has promising potential as a potent, selective, and low-brain-penetrating agonist for BB(3) and BB(3) could potentially be a valuable treatment target for type 2 diabetes mellitus.
Pubmed: 37272653   DOI: 10.1021/acs.jmedchem.3c00323