mProX™ Human HCAR2 Stable Cell Line

Kao KD, et al. "The Cxcr2(+) subset of the S100a8(+) gastric granylocytic myeloid-derived ." Frontiers in immunology, 2023.
Gastric myeloid-derived suppressor cells (MDSCs) have been identified as a prominent population that expands during gastric pre-neoplastic and neoplastic development in both humans and mice. However, the heterogeneity of this population has made it difficult to study and understand its functions. A specific subset of these cells, known as Schlafen-4(+) (Slfn-4(+)) MDSCs, has been studied in mouse models. Despite this, there is still limited knowledge on the heterogeneity of the gastric CD11b(+)Ly6G(+) population and how to target its various subsets. To address this, researchers have identified S100a8 as a pan-specific marker for this population. They utilized this marker to study the role of the S100a8(+)Cxcr2(+) subset and found that it plays a significant role in regulating gastric immunopathology and lipid peroxidation. This was determined through transcriptomic and single-cell RNA sequencing of gastric CD11b(+)Ly6G(+) cells and the generation of S100a8(Cre)Cxcr2(flox/flox) mice. These findings provide valuable insight into the heterogeneity and functions of gastric MDSCs, highlighting the potential use of S100a8 as a target for future studies.
Pubmed: 37744359   DOI: 10.3389/fimmu.2023.1147695

Cheng L, et al. "Orthosteric ligand selectivity and allosteric probe dependence at ." Signal transduction and targeted therapy, 2023.
Hydroxycarboxylic acid receptor 2 (HCAR2) is a Class A G-protein-coupled receptor (GPCR) that has significant therapeutic potential in the treatment of dyslipidemia and inflammatory diseases due to its anti-lipolytic and anti-inflammatory effects. However, the signaling mechanism of HCAR2 induced by different ligands remains unclear. In this study, the authors present a cryo-electron microscopy (cryo-EM) structure of G(i)-coupled HCAR2 in complex with a selective agonist, MK-6892, at a resolution of 2.60 A. The authors' structural analysis shows that MK-6892 occupies both the orthosteric binding pocket (OBP) and an extended binding pocket (EBP) within HCAR2. Pharmacological assays reveal that the OBP is crucial for ligand selectivity among the HCAR subfamily. Additionally, the authors investigate the effects of the allosteric modulator compound 9n on HCAR2, demonstrating its probe-dependent behavior in response to different orthosteric agonists. These findings provide fundamental insights into the regulatory mechanisms of HCAR2 signaling mediated by both orthosteric and allosteric ligands.
Pubmed: 37743365   DOI: 10.1038/s41392-023-01625-y