1,285 results match your criteria receptor-mediated signalling


Bradykinin Protects Human Endothelial Progenitor Cells from High-Glucose-Induced Senescence through B2 Receptor-Mediated Activation of the Akt/eNOS Signalling Pathway.

J Diabetes Res 2021 11;2021:6626627. Epub 2021 Sep 11.

Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Background: Circulating endothelial progenitor cells (EPCs) play important roles in vascular repair. However, the mechanisms of high-glucose- (HG-) induced cord blood EPC senescence and the role of B2 receptor (B2R) remain unknown.

Methods: Cord blood samples from 26 patients with gestational diabetes mellitus (GDM) and samples from 26 healthy controls were collected. Read More

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September 2021

Generation of stable cell lines using readthrough expression from lentiviral integration.

Biotechnol Lett 2021 Sep 17. Epub 2021 Sep 17.

Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada.

Lentiviral infection is often used to integrate genetic material into cells to stably express transgenes of interest. Depending on the location of integration into the host genome, readthrough expression of the lentiviral cargo can occur via an upstream endogenous promoter, which is typically an unwanted phenomenon because it can result in dysfunctional expression. The purpose of this study was to demonstrate that readthrough expression can be a wanted phenomenon for expressing functional proteins while at the same time reducing the size of the lentiviral transfer plasmid. Read More

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September 2021

Open Biology: overview for special issue on dynamics of protein fatty acylation.

Authors:
Marilyn D Resh

Open Biol 2021 Sep 15;11(9):210228. Epub 2021 Sep 15.

Cell Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 143, New York, NY 10075, USA.

Fatty acylation is a widespread form of protein modification that occurs on specific intracellular and secreted proteins. Beyond increasing hydrophobicity and the affinity of the modified protein for lipid bilayers, covalent attachment of a fatty acid exerts effects on protein localization, inter- and intramolecular interactions and signal transduction. As such, research into protein fatty acylation has been embraced by an extensive community of biologists. Read More

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September 2021

Apomorphine Reduces A53T α-Synuclein-Induced Microglial Reactivity Through Activation of NRF2 Signalling Pathway.

Cell Mol Neurobiol 2021 Aug 20. Epub 2021 Aug 20.

Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365, Esch-sur-Alzette, Luxembourg.

The chiral molecule, apomorphine, is currently used for the treatment of Parkinson's disease (PD). As a potent dopamine receptor agonist, this lipophilic compound is especially effective for treating motor fluctuations in advanced PD patients. In addition to its receptor-mediated actions, apomorphine has also antioxidant and free radical scavenger activities. Read More

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X-linked serotonin 2C receptor is associated with a non-canonical pathway for sudden unexpected death in epilepsy.

Brain Commun 2021 9;3(3):fcab149. Epub 2021 Jul 9.

Developmental Neurogenetics Laboratory, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.

Sudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Read More

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Dopaminergic mechanisms underlying the expression of antipsychotic-induced dopamine supersensitivity in rats.

Neuropharmacology 2021 Oct 5;197:108747. Epub 2021 Aug 5.

Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, 2900 Edouard-Montpetit boulevard, Montreal, H3T 1J4, Quebec, Canada; Groupe de recherche sur le système nerveux central, Faculty of Medicine, Université de Montréal, 2900 Edouard-Montpetit boulevard, Montrea, H3T 1J4, Quebec, Canada. Electronic address:

Antipsychotic treatment can produce a dopamine-supersensitive state, potentiating the response to dopamine receptor stimulation. In both schizophrenia patients and rats, this is linked to tolerance to ongoing antipsychotic treatment. In rodents, dopamine supersensitivity is often confirmed by an exaggerated psychomotor response to d-amphetamine after discontinuation of antipsychotic exposure. Read More

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October 2021

Recent Insights into the Interplay of Alpha-Synuclein and Sphingolipid Signaling in Parkinson's Disease.

Int J Mol Sci 2021 Jun 11;22(12). Epub 2021 Jun 11.

Laboratory of Preclinical Research and Environmental Agents, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego St., 02-106 Warsaw, Poland.

Molecular studies have provided increasing evidence that Parkinson's disease (PD) is a protein conformational disease, where the spread of alpha-synuclein (ASN) pathology along the neuraxis correlates with clinical disease outcome. Pathogenic forms of ASN evoke oxidative stress (OS), neuroinflammation, and protein alterations in neighboring cells, thereby intensifying ASN toxicity, neurodegeneration, and neuronal death. A number of evidence suggest that homeostasis between bioactive sphingolipids with opposing function-e. Read More

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The contact system in liver injury.

Semin Immunopathol 2021 Aug 14;43(4):507-517. Epub 2021 Jun 14.

Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.

Coagulation is controlled by a delicate balance of prothrombotic and antithrombotic mechanisms, to prevent both excessive blood loss from injured vessels and pathologic thrombosis. The liver plays a pivotal role in hemostasis through the synthesis of plasma coagulation factors and their inhibitors that, in addition to thrombosis and hemostasis, orchestrates an array of inflammatory responses. As a result, impaired liver function has been linked with both hypercoagulability and bleeding disorders due to a pathologic balance of pro- and anticoagulant plasma factors. Read More

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Courier service for phosphatidylinositol: PITPs deliver on demand.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 09 7;1866(9):158985. Epub 2021 Jun 7.

Dept. of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, UK. Electronic address:

Phosphatidylinositol is the parent lipid for the synthesis of seven phosphorylated inositol lipids and each of them play specific roles in numerous processes including receptor-mediated signalling, actin cytoskeleton dynamics and membrane trafficking. PI synthesis is localised to the endoplasmic reticulum (ER) whilst its phosphorylated derivatives are found in other organelles where the lipid kinases also reside. Phosphorylation of PI to phosphatidylinositol (4,5) bisphosphate (PI(4,5)P) at the plasma membrane and to phosphatidylinositol 4-phosphate (PI4P) at the Golgi are key events in lipid signalling and Golgi function respectively. Read More

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September 2021

Sex-specific plasticity in CRF regulation of inhibitory control in central amygdala CRF1 neurons after chronic voluntary alcohol drinking.

Addict Biol 2021 Jun 2:e13067. Epub 2021 Jun 2.

Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.

Despite strong preclinical evidence for the ability of corticotropin releasing factor 1 (CRF1) antagonists to regulate alcohol consumption, clinical trials have not yet demonstrated therapeutic effects of these compounds in alcohol use disorder (AUD) patients. Several confounding factors may limit the translation of preclinical CRF1 research to patients, including reliance on experimenter-administered alcohol instead of voluntary consumption, a preponderance of evidence collected in male subjects only and an inability to assess the effects of alcohol on specific brain circuits. A population of particular interest is the CRF1-containing neurons of the central amygdala (CeA). Read More

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Purinergic P2 and glutamate NMDA receptor coupling contributes to osmotically driven excitability in hypothalamic magnocellular neurosecretory neurons.

J Physiol 2021 07 26;599(14):3531-3547. Epub 2021 Jun 26.

Neuroscience Institute, Georgia State University, Atlanta, Georgia, USA.

Key Points: Purinergic and glutamatergic signalling pathways play a key role in regulating the activity of hypothalamic magnocellular neurosecretory neurons (MNNs). However, the precise cellular mechanisms by which ATP and glutamate act in concert to regulate osmotically driven MNN neuronal excitability remains unknown. Here, we report that ATP acts on purinergic P2 receptors in MNNs to potentiate in a Ca -dependent manner extrasynaptic NMDAR function. Read More

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Biased agonists with less glucagon-like peptide-1 receptor-mediated endocytosis prolong hypoglycaemic effects.

Eur J Pharmacol 2021 Sep 26;907:174203. Epub 2021 May 26.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:

Receptor endocytic trafficking entails targeting receptors and ligands to endocytic sites, followed by internalization and sorting to recycling or degradative compartments. Thus, membrane receptor-mediated signalling pathways not only contribute to the efficacy of the drugs but also play a crucial role in the metabolic elimination of peptide drugs. Glucagon-like peptide-1 (GLP-1) receptor is the crucial target for type 2 diabetes mellitus. Read More

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September 2021

Increasing Efficiency of Repetitive Electroacupuncture on Purine- and Acid-Induced Pain During a Three-Week Treatment Schedule.

Front Pharmacol 2021 10;12:680198. Epub 2021 May 10.

School of Acupuncture and Tuina, Chengdu University of Traditional Medicine, Chengdu, China.

Acupuncture (AP) is an important constituent of the therapeutic repertoire of traditional Chinese medicine and has been widely used to alleviate chronic painful conditions all over the world. We studied in rats the efficiency of electroacupuncture (EAP) applied to the Zusanli acupoint (ST36) as an analgesic treatment over a 3-week period of time on purine (α,β-methylene ATP, dibenzoyl-ATP)- and acid (pH 6.0 medium)-induced pain in the rat paw. Read More

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Protein tyrosine phosphatase receptor type C (PTPRC or CD45).

J Clin Pathol 2021 Sep 26;74(9):548-552. Epub 2021 May 26.

Patrick G Johnston Centre for Cancer Research (PGJCCR), Queen's University Belfast, Belfast, UK.

The leucocyte common antigen, protein tyrosine phosphatase receptor type C (PTPRC), also known as CD45, is a transmembrane glycoprotein, expressed on almost all haematopoietic cells except for mature erythrocytes, and is an essential regulator of T and B cell antigen receptor-mediated activation. Disruption of the equilibrium between protein tyrosine kinase and phosphatase activity (from CD45 and others) can result in immunodeficiency, autoimmunity, or malignancy. CD45 is normally present on the cell surface, therefore it works upstream of a large signalling network which differs between cell types, and thus the effects of CD45 on these cells are also different. Read More

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September 2021

Glucose and NAADP trigger elementary intracellular β-cell Ca signals.

Sci Rep 2021 05 21;11(1):10714. Epub 2021 May 21.

Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, UK.

Pancreatic β-cells release insulin upon a rise in blood glucose. The precise mechanisms of stimulus-secretion coupling, and its failure in Diabetes Mellitus Type 2, remain to be elucidated. The consensus model, as well as a class of currently prescribed anti-diabetic drugs, are based around the observation that glucose-evoked ATP production in β-cells leads to closure of cell membrane ATP-gated potassium (K) channels, plasma membrane depolarisation, Ca influx, and finally the exocytosis of insulin granules. Read More

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P2X7 Receptor-Mediated Inflammation in Cardiovascular Disease.

Front Pharmacol 2021 29;12:654425. Epub 2021 Apr 29.

School of Acupuncture and Tuina and International Collaborative Centre on Big Science Plan for Purinergic Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Purinergic P2X7 receptor, a nonselective cation channel, is highly expressed in immune cells as well as cardiac smooth muscle cells and endothelial cells. Its activation exhibits to mediate nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome activation, resulting in the release of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), and pyroptosis, thus triggering inflammatory response. These pathological mechanisms lead to the deterioration of various cardiovascular diseases, including atherosclerosis, arrhythmia, myocardial infarction, pulmonary vascular remodeling, and cardiac fibrosis. Read More

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Microglia-leucocyte axis in cerebral ischaemia and inflammation in the developing brain.

Acta Physiol (Oxf) 2021 09 30;233(1):e13674. Epub 2021 May 30.

Department of Neurology, University of California San Francisco, San Francisco, CA, USA.

Development of the Central Nervous System (CNS) is reliant on the proper function of numerous intricately orchestrated mechanisms that mature independently, including constant communication between the CNS and the peripheral immune system. This review summarizes experimental knowledge of how cerebral ischaemia in infants and children alters physiological communication between leucocytes, brain immune cells, microglia and the neurovascular unit (NVU)-the "microglia-leucocyte axis"-and contributes to acute and long-term brain injury. We outline physiological development of CNS barriers in relation to microglial and leucocyte maturation and the plethora of mechanisms by which microglia and peripheral leucocytes communicate during postnatal period, including receptor-mediated and intracellular inflammatory signalling, lipids, soluble factors and extracellular vesicles. Read More

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September 2021

IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection.

Nat Microbiol 2021 07 13;6(7):932-945. Epub 2021 May 13.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

The retinoic acid-inducible gene I (RIG-I) receptor senses cytoplasmic viral RNA and activates type I interferons (IFN-I) and downstream antiviral immune responses. How RIG-I binds to viral RNA and how its activation is regulated remains unclear. Here, using IFI16 knockout cells and p204-deficient mice, we demonstrate that the DNA sensor IFI16 enhances IFN-I production to inhibit influenza A virus (IAV) replication. Read More

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Iron induces two distinct Ca signalling cascades in astrocytes.

Commun Biol 2021 05 5;4(1):525. Epub 2021 May 5.

Practical Teaching Centre, School of Forensic Medicine, China Medical University, Shenyang, PR China.

Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca]) in astrocytes. Read More

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The therapeutic potential of GLP-1 receptor biased agonism.

Authors:
Ben Jones

Br J Pharmacol 2021 Apr 20. Epub 2021 Apr 20.

Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective treatments for type 2 diabetes as they stimulate insulin release and promote weight loss through appetite suppression. Their main side effect is nausea. All approved GLP-1 agonists are full agonists across multiple signalling pathways. Read More

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Involvement of TRPC5 channels, inwardly rectifying K channels, PLCβ and PIP in vasopressin-mediated excitation of medial central amygdala neurons.

J Physiol 2021 06 27;599(12):3101-3119. Epub 2021 Apr 27.

Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58203, USA.

Key Points: Activation of V vasopressin receptors facilitates neuronal excitability in the medial nucleus of central amygdala (CeM) V receptor activation excites about 80% CeM neurons by opening a cationic conductance and about 20% CeM neurons by suppressing an inwardly rectifying K (Kir) channel The cationic conductance activated by V receptors is identified as TRPC5 channels PLCβ-mediated depletion of PIP is involved in V receptor-elicited excitation of CeM neurons Intracellular Ca release and PKC are unnecessary for V receptor-mediated excitation of CeM neurons ABSTRACT: Arginine vasopressin (AVP) serves as a hormone in the periphery to modulate water homeostasis and a neuromodulator in the brain to regulate a diverse range of functions including anxiety, social behaviour, cognitive activities and nociception. The amygdala is an essential brain region involved in modulating defensive and appetitive behaviours, pain and alcohol use disorders. Whereas activation of V receptors in the medial nucleus of the central amygdala (CeM) increases neuronal excitability, the involved ionic and signalling mechanisms have not been determined. Read More

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Adenosine and adenosine receptor-mediated action in coronary microcirculation.

Basic Res Cardiol 2021 03 23;116(1):22. Epub 2021 Mar 23.

Division of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 17176, Stockholm, Sweden.

Adenosine is an ubiquitous extracellular signaling molecule and plays a fundamental role in the regulation of coronary microcirculation through activation of adenosine receptors (ARs). Adenosine is regulated by various enzymes and nucleoside transporters for its balance between intra- and extracellular compartments. Adenosine-mediated coronary microvascular tone and reactive hyperemia are through receptors mainly involving AR activation on both endothelial and smooth muscle cells, but also involving interaction among other ARs. Read More

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The S6k/4E-BP mediated growth promoting sub-pathway of insulin signalling cascade is essential to restrict pathogenesis of poly(Q) disorders in Drosophila.

Life Sci 2021 Jun 18;275:119358. Epub 2021 Mar 18.

Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, India. Electronic address:

Human neurodegenerative polyglutamine [poly(Q)] disorders, such as Huntington's disease (HD) and spinocerebellar ataxias (SCA), are characterised by an abnormal expansion of CAG repeats in the affected gene. The mutated proteins misfold and aggregate to form inclusion bodies that sequester important factors involved in cellular transcription, growth, stress and autophagic response and other essential functions. The insulin signalling pathway has been demonstrated as a major modifier and a potential drug target to ameliorate the poly(Q) mediated neurotoxicity in various model systems. Read More

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Multi-organ coordination of lipoprotein secretion by hormones, nutrients and neural networks.

Endocr Rev 2021 Mar 20. Epub 2021 Mar 20.

Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.

Plasma triglyceride-rich lipoproteins (TRL), particularly atherogenic remnant lipoproteins, contribute to atherosclerotic cardiovascular disease (ASCVD). Hypertriglyceridemia may arise in part from hypersecretion of TRLs by the liver and intestine. Here we focus on the complex network of hormonal, nutritional, and neuronal interorgan communication that regulates secretion of TRLs, and provide our perspective on the relative importance of these factors. Read More

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Non-peptide agonists and positive allosteric modulators of glucagon-like peptide-1 receptors: Alternative approaches for treatment of Type 2 diabetes.

Br J Pharmacol 2021 Mar 16. Epub 2021 Mar 16.

Department of Chemistry and Biochemistry, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA.

Glucagon-like peptide-1 (GLP-1) receptors belong to the pharmaceutically important Class B family of GPCRs and are involved in many biologically significant signalling pathways. Its incretin peptide ligand GLP-1 analogues are effective treatments for Type 2 diabetes. Although developing non-peptide low MW drugs targeting GLP-1 receptors remains elusive, considerable progress has been made in discovering non-peptide agonists and positive allosteric modulators (PAMs) of GLP-1 receptors with demonstrated efficacy. Read More

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PAC1 Receptor Internalization and Endosomal MEK/ERK Activation Is Essential for PACAP-Mediated Neuronal Excitability.

J Mol Neurosci 2021 Aug 6;71(8):1536-1542. Epub 2021 Mar 6.

Departmental of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA.

Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) can significantly increase the excitability of diverse neurons through differential mechanisms. For guinea pig cardiac neurons, the modulation of excitability can be mediated in part by PAC1 receptor plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. By contrast, PAC1 receptor-mediated excitability of hippocampal dentate gyrus granule cells appears independent of membrane-delimited AC/cAMP/PKA and PLC/PKC signaling. Read More

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AQP8 participates in oestrogen-mediated buffalo follicular development by regulating apoptosis of granulosa cells.

Reprod Domest Anim 2021 May 9;56(5):812-820. Epub 2021 Mar 9.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, Nanning, China.

Aquaporins (AQPs), a family of small membrane-spanning proteins, are involved in fluid transport, cell signalling and reproduction. Regulating AQP8 expression influences apoptosis of granulosa cells (GCs), ovarian folliculogenesis, oogenesis and early embryonic development in mice, but its role has never been investigated in other species. The aim of the present study was to characterize the AQP8 function in buffalo follicular development. Read More

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A Phase I/II Clinical Trial to evaluate the efficacy of baricitinib to prevent respiratory insufficiency progression in onco-hematological patients affected with COVID19: A structured summary of a study protocol for a randomised controlled trial.

Trials 2021 Feb 5;22(1):116. Epub 2021 Feb 5.

Intensive Care Department, Hospital Universitari de Bellvitge, L'Hospitalet de LL., Barcelona, Spain.

Objectives: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. Read More

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February 2021

SGIP1 is involved in regulation of emotionality, mood, and nociception and modulates in vivo signalling of cannabinoid CB receptors.

Br J Pharmacol 2021 04 27;178(7):1588-1604. Epub 2021 Feb 27.

Department of Molecular Pharmacology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague 4, Czech Republic.

Background And Purpose: Src homology 3-domain growth factor receptor-bound 2-like endophilin interacting protein 1 (SGIP1) interacts with cannabinoid CB receptors. SGIP1 is abundantly and principally expressed within the nervous system. SGIP1 and CB receptors co-localize in axons and presynaptic boutons. Read More

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The G Protein-Coupled Receptor Kinases (GRKs) in Chemokine Receptor-Mediated Immune Cell Migration: From Molecular Cues to Physiopathology.

Cells 2021 01 5;10(1). Epub 2021 Jan 5.

Inflammation Chemokines and Immunopathology, INSERM, UMR 996, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 92140 Clamart, France.

Although G protein-coupled receptor kinases (GRKs) have long been known to regulate G protein-coupled receptor (GPCR) desensitization, their more recently characterized functions as scaffolds and signalling adapters underscore that this small family of proteins governs a larger array of physiological functions than originally suspected. This review explores how GRKs contribute to the complex signalling networks involved in the migration of immune cells along chemokine gradients sensed by cell surface GPCRs. We outline emerging evidence indicating that the coordinated docking of several GRKs on an active chemokine receptor determines a specific receptor phosphorylation barcode that will translate into distinct signalling and migration outcomes. Read More

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January 2021