Article
Oncology
Elzbieta Pawluczuk, Marta Lukaszewicz-Zajac, Mariusz Gryko, Agnieszka Kulczynska-Przybik, Barbara Mroczko
Summary: The study suggests that serum CXCL8 and CXCR2 concentrations are significantly higher in gastric cancer patients compared to healthy controls, with CXCL8 showing the highest diagnostic sensitivity among all tested proteins. Serum CXCL8 levels are indicated as a significant risk factor for gastric cancer occurrence and are a promising candidate for a biomarker in gastric cancer diagnosis.
Article
Biochemistry & Molecular Biology
Melissa Girard, Steve Dagenais Bellefeuille, Emilie Eiselt, Guillaume Arguin, Jean-Michel Longpre, Philippe Sarret, Fernand-Pierre Gendron
Summary: This study found that endosomal trafficking plays an important role in G protein-coupled receptor (GPCR) signaling. UDP selectively activates GPCR P2Y6 as a signaling molecule. The study found that MRS2693 and UDP have different effects on the internalization of the P2Y6 receptor, with MRS2693 inducing P2Y6 internalization through an independent caveolin-dependent mechanism. This study provides insights for the development of bias ligands that can influence P2Y6 signaling.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Review
Medicine, Research & Experimental
Juan Carlos Martinez-Morales, K. Helivier Solis, M. Teresa Romero-Avila, Guadalupe Reyes-Cruz, J. Adolfo Garcia-Sainz
Summary: G protein-coupled receptors (GPCRs) are membrane proteins that function as sensors and play significant roles in various physiological and pathological processes. This review provides an overview of the current understanding of the structure, signaling, internalization, and recycling of GPCRs.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Review
Immunology
Nan Li, Shan Shan, Xiu-Qin Li, Ting-Ting Chen, Meng Qi, Sheng-Nan Zhang, Zi-Ying Wang, Ling-Ling Zhang, Wei Wei, Wu-Yi Sun
Summary: G protein-coupled receptor kinase 2 (GRK2) plays important roles in regulating signaling pathways associated with fibrotic diseases. Recent research suggests that GRK2 could be a potential therapeutic target for fibrotic diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Kawthar Dhayni, Kazem Zibara, Hawra Issa, Said Kamel, Youssef Bennis
Summary: CXCR1 and CXCR2 chemokine receptors are critical in inflammation, and CXCR1/2 inhibitors show beneficial effects in preventing cardiovascular disease progression.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Oncology
Marta Smycz-Kubanska, Sebastian Stepien, Joanna Magdalena Gola, Celina Kruszniewska-Rajs, Dominika Wendlocha, Patrycja Krolewska-Daszczynska, Anna Strzelec, Jaroslaw Strzelczyk, Wojciech Szanecki, Andrzej Witek, Aleksandra Mielczarek-Palacz
Summary: Understanding the relationship between inflammatory and neoplastic processes in ovarian cancer, particularly chemokines and their receptors. Analyzing the levels of CXCL8 and its receptors CXCR1 and CXCR2 in serum and peritoneal fluid, and evaluating the association with tumor tissue and patient characteristics. The involvement of CXCL8 and its receptors in the pathogenesis of ovarian cancer indicates potential clinical applications.
MOLECULAR MEDICINE REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Zhi-Jian Han, Yang-Bing Li, Lu-Xi Yang, Hui-Juan Cheng, Xin Liu, Hao Chen
Summary: Interleukin-8 (IL-8 or CXCL8) plays multiple roles within the tumor microenvironment (TME), affecting various components of TME and influencing tumor progression and therapeutic resistance. CXCL8 could be used as a prognostic biomarker and targeting the CXCL8-CXCR1/2 axis shows promise in improving antitumor efficacy. Understanding the interactions between TME components and the CXCL8-CXCR1/2 axis is important for developing novel immunotherapy strategies.
Review
Endocrinology & Metabolism
Fanhua Wang, Mingyao Liu, Ning Wang, Jian Luo
Summary: This review discusses the role of G-protein coupled receptors (GPCRs) in osteoarthritis (OA), including the pathophysiological processes involved, preclinical and clinical trial data, and the challenges in developing therapies targeting GPCRs for OA.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Pharmacology & Pharmacy
Kate F. Byrne, Ajay Pal, James F. Curtin, John C. Stephens, Gemma K. Kinsella
Summary: The focus of the review is on G-protein-coupled receptor (GPCR) targets, with chemokine, cannabinoid, and dopamine receptors showing promise. Further research is needed on potential targets such as MC4R, adhesion receptors, LPA, and Smo receptors to develop new drug-screening strategies for safe and effective GBM therapies.
DRUG DISCOVERY TODAY
(2021)
Review
Biochemistry & Molecular Biology
Dekel David, Ziv Bentulila, Merav Tauber, Yair Ben-Chaim
Summary: GPCRs are involved in signal transduction processes, and although they span the cell membrane, they have not been considered to be regulated by membrane potential. Recent studies, however, have shown that several GPCRs are voltage regulated. This review discusses the advances in understanding the voltage dependence of GPCRs, the suggested molecular mechanisms, and the possible physiological roles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Ramon Cierco Jimenez, Nil Casajuana-Martin, Adrian Garcia-Recio, Lidia Alcantara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez
Summary: The study analyzed 119,069 natural variants in human olfactory receptors, revealing a significant diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a considerable number of changes occurring at the structurally conserved regions. Mutations in positions linked to the conserved GPCR activation mechanism were highlighted, which could imply phenotypic variation in olfactory perception.
Review
Chemistry, Multidisciplinary
Bingjie Zhang, Shanshan Li, Wenqing Shui
Summary: G protein-coupled receptors (GPCRs) are a large family of proteins that play significant roles in cellular and physiological responses. Post-translational modifications (PTMs) of GPCRs, such as glycosylation, phosphorylation, ubiquitination and palmitoylation, have important regulatory functions in receptor folding, biosynthesis, trafficking, dimerization and signaling. This review provides an overview of PTMs in GPCRs, focusing on their types, locations, cross talk and dynamic regulation, which can shed light on the molecular basis of GPCRs and contribute to structure-based drug discovery.
FRONTIERS IN CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Chemistry, Multidisciplinary
Xin-heng He, Chong-zhao You, Hua-liang Jiang, Yi Jiang, H. Eric Xu, Xi Cheng
Summary: G protein-coupled receptors (GPCRs) are important drug targets that play crucial roles in various physiological processes. Although extensive efforts have been made in the field of structural biology, a significant number of GPCR structures remain unsolved due to their structural instability. Recently, AlphaFold2 has been developed as a tool to predict the structure models of GPCRs and other functionally important proteins. However, our evaluation reveals several differences between the predicted models and experimental structures, such as the assembly of domains, shape of ligand-binding pockets, and conformation of binding interfaces. These differences hinder the use of predicted structure models in functional studies and structure-based drug design, where reliable high-resolution structural information is required.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Wojciech Pietrus, Rafal Kurczab, Dagmar Stumpfe, Andrzej J. Bojarski, Juergen Bajorath
Summary: The study showed that introducing fluorine can significantly increase ligand potency, but the effect of fluorination on affinity varies depending on the fluorination position. Fluorination of the aromatic ring at the ortho position is favorable for potency enhancement, while fluorination of aliphatic fragments more often leads to a decrease in biological activity.