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Here we report that neuropeptide S (NPS) signaling in the PVT is necessary for stimulus salience encoding

biotech company with a unique portfolio of CB1 inverse agonists, today announces the appointment of Glenn S. Vraniak served as Chief Financial Officer of Evaxion Biotech A/S, an AI enabled immuno-oncology company

November 2021 Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 GPCRs steer G i and G s selectivity via TM5-TM6 switches as revealed by structures of serotonin

Objective: The goal of this study was to determine the glucometabolic effects of acute activation of Gs signaling in skeletal muscle (SKM) in vivo and its contribution to whole-body glucose homeostasis. Methods: To address this question, we studied mice that express a Gs-coupled designer G protein-coupled receptor (Gs-DREADD or GsD) selectively in skeletal muscle. We also identified two Gs-coupled GPCRs that are endogenously expressed by SKM at relatively high levels (β2-adrenergic receptor and CRF2 receptor) and studied the acute metabolic effects of activating these receptors in vivo by highly selective agonists (clenbuterol and urocortin 2 (UCN2), respectively). Results: Acute stimulation of GsD signaling in SKM impaired glucose tolerance in lean and obese mice by decreasing glucose uptake selectively into SKM. The acute metabolic effects following agonist activation of β2-adrenergic and, potentially, CRF2 receptors appear primarily mediated by altered insulin release. Clenbuterol injection improved glucose tolerance by increasing insulin secretion in lean mice. In SKM, clenbuterol stimulated glycogen breakdown. UCN2 injection resulted in decreased glucose tolerance associated with lower plasma insulin levels. The acute metabolic effects of UCN2 were not mediated by SKM Gs signaling. Conclusions: Selective activation of Gs signaling in SKM causes an acute increase in blood glucose levels. However, acute in vivo stimulation of endogenous Gs-coupled receptors enriched in SKM has only a limited impact on whole-body glucose homeostasis, most likely due to the fact that these receptors are also expressed by pancreatic islets where they modulate insulin release. Read full article

HBx-induced cell cycle acceleration and the subsequent proliferative response via the induction of G1/S transcription factor 1; FBS: fetal bovine serum; GPCRs: G protein-coupled receptors; GST: glutathione S-transferase

Here, we discuss recent crystal structures of inactive C5aR1 in terms of an inverted orientation of helix

September 2022 Lysine 101 in the CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal residue in a cholesterol recognition/interaction amino acid consensus (CRAC) motif in transmembrane helix

April is the month of DNA Day, a special day commemorating the discovery of the DNA double helix structure S. (2002) National Human Genome Research Institute. S., Caron, M. G., Lefkowitz, R. J., & Strader, C. D. (1986). Molecular pharmacology, 63(6), 1256–1272. https://doi.org/10.1124/mol.63.6.1256 Syed Haneef, S. ., & Ranganathan, S. (2019). Structural bioinformatics analysis of variants on GPCR function.

S., Vojtek, M., Sousa, J. B., & Diniz, C. (2021). , S. K., Karnik, S. S., Hunyady, L., Luttrell, L. M., & Lefkowitz, R. J. (2003). , Volpe, S., Werthmann, R. A., Sriram, K., Wiley, S.

., Odongo, S., Radwanska, M., & Magez, S. (2023). pharmacology and toxicology, 57, 19–37. https://doi.org/10.1146/annurev-pharmtox-010716-104710 Rasmussen, S. S., Devree, B. T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. K., Gellman, S. H., Pautsch, A., Steyaert, J., Weis, W. S., Ingram, J. R., Venkatakrishnan, A. J., Jude, K. M., Dukkipati, A., Feinberg, E.

., & Kongsamut, S. (2013). Minireview: targeting GPCR activated ERK pathways for drug discovery. Wei, H., Ahn, S., Shenoy, S. K., Karnik, S. S., Hunyady, L., Luttrell, L. M., & Lefkowitz, R.

Yamaguchi S, Kaneko M, Narukawa M. Liu S, Anderson PJ, Rajagopal S, Lefkowitz RJ, Rockman HA. Lu S, He X, Ni D, Zhang J. Shen S, Zhao C, Wu C, Sun S, Li Z, Yan W, et al. Teng X, Chen S, Wang Q, Chen Z, Wang X, Huang N, et al.

Agonist activation of the β2-adrenoceptor (β2AR) causes its S-nitrosylation that is required for the Eliminating β2AR S-nitrosylation by mutation of C265 augments β2AR protein kinase A signaling, enables

From the initial GTP binding, the structures highlight critical shifts in the α5 helix and the α-helical Concurrently, the α1 helix extends, propagating structural changes throughout the G protein. The AHD transitioning to a closed conformation prompts the β2–β3 loop to move away from the α5 helix, disrupting an ionic lock and allowing the α5 helix to start transitioning. This helix undergoes significant restructuring—it breaks and reforms closer to the TCAT motif, which

Notably, the Y320F mutation restored some signaling capabilities, emphasizing Tyr320's role in membrane Reference Roy, S., Sinha, S., Silas, A. J., Ghassemian, M., Kufareva, I., & Ghosh, P. (2024).

resonance energy transfer (FRET) has revealed that GLP-1R homodimerization occurs via transmembrane helix Proc Natl Acad Sci U S A, 2012. 109 (45): p. 18607-12. 8.         

signaling, they also influence specific pathways such as MAPK signaling (Song, X. et al. 2009, Coffa, S. S. F et al. 2021, Chen, H. et al. 2022). point of origin, suggesting the formation of active "nano domains" in specific membrane niches (Anton, S. S. et al. 2022). S. F. et al. 2021).

First, we switched GPCRs between S. pombe and the closely related species Schizosaccharomyces octosporus , which showed that SoMam2 (Mam2 of S. octosporus) is partially functional in S. pombe, whereas SoMap3 (Map3 of S. octosporus) is not interchangeable.

TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. However, a clear picture is needed to unravel TRPM3's full potential as experimental tool, diagnostic

while maintaining the responsiveness of canonical G protein-coupled CKRs that bind to the same ligand(s) example of a dual-function receptor that directly regulates both cell migration and scavenging (Volpe S.

., Trumpp-Kallmeyer, S., & Humblet, C. (1998). B., Chang, B., & Peisajovich, S. G. (2017). M., & Fields, S. (2014). Deep mutational scanning: a new style of protein science.

August 2022 "Aims: The pathophysiological mechanism(s) underlying non-alcoholic fatty liver disease (

., O'Brien, S. L., Stepniewski, T. K., Selent, J., Hill, S. J., & Calebiro, D. (2023). M., Kawakami, K., Masureel, M., Maeda, S., Garcia, K. C., von Zastrow, M., Inoue, A., & Kobilka, B. Reiter, E., Ahn, S., Shukla, A.K., and Lefkowitz, R.J. (2012).

This study examines these concerns by comparing AF2's predictions with experimental structures for docking This validates AF2's potential in enhancing drug discovery precision and efficiency.

express multiple ORs, tumor cells associated with the nervous system express a single OR gene type (Kalra S. Al 2017) and its activation promotes migration and angiogenesis (Kim S. et. al 2015). OR2AT4 activation leads to reduced proliferation and enhanced apoptosis of acute myeloid leukemia cells (S cells proliferation via activation by β-ionone which initiates prostate cancer cell cycle arrest (Jones S.

the responsiveness of canonical G protein–coupled chemokine receptors that bind to the same ligand(s) an example of a dual-function receptor that directly regulates both cell migration and scavenging (S. Grundmann et al. 2018), did not affect chemokine scavenging, consistent with prior work (S. Scavenging may allow cells to continuously migrate by remaining responsive to chemokines (S.

However, GRK3’s functions and clinical utility in GAC progression and metastases are unknown.