A5055107010- Chemokine receptors and signaling
- Receptor Mechanisms and Signaling
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Exercise and Physiological Responses
- Protein purification and stability
- Transgenic Plants and Applications
- Pain Mechanisms and Treatments
- DNA Repair Mechanisms
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Ion Channels and Receptors
- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Mitochondrial Function and Pathology
- Neuropeptides and Animal Physiology
- Fungal and yeast genetics research
- Estrogen and related hormone effects
- Computational Drug Discovery Methods
- Cytokine Signaling Pathways and Interactions
- Molecular Biology Techniques and Applications
- Acute Myeloid Leukemia Research
Friedrich Schiller University Jena
2018-2024
Vrije Universiteit Amsterdam
2020-2024
Luxembourg Institute of Health
2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2024
University of Würzburg
2017-2023
University of Birmingham
2019-2020
University of Nottingham
2019-2020
Max Delbrück Center
2019-2020
Queen's Medical Centre
2020
Jena University Hospital
2020
Atypical chemokine receptor 3 (ACKR3), formerly referred to as CXCR7, is considered be an interesting drug target. In this study, we report on the synthesis, pharmacological characterization and radiolabeling of VUF15485, a new ACKR3 small-molecule agonist, that will serve important tool study <i>β</i>-arrestin-biased receptor. VUF15485 binds with nanomolar affinity (pIC<sub>50</sub> = 8.3) human ACKR3, measured in [<sup>125</sup>I]CXCL12 competition binding experiments. Moreover,...
Significance Class A G protein−coupled receptors (GPCRs) can form dimers and oligomers via poorly understood mechanisms. We show here that the chemokine receptor CXCR4, which is a major pharmacological target, has an oligomerization behavior modulated by its active conformation. Combining advanced, single-molecule, single-cell optical tools with functional assays computational approaches, we unveil three key features of CXCR4 quaternary organization: dimerization 1) dynamic, 2) increases...
Antinociceptive pathways are activated in the periphery inflammatory pain, for instance resolvins and opioid peptides. Resolvins biosynthesized from omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid docosahexaenoic acid. Resolvin D1 (RvD1) resolvin E1 (RvE1) initiate resolution of inflammation control hypersensitivity via induction anti-inflammatory signaling cascades. RvD1 binds to lipoxin A4/annexin-A1 receptor/formyl-peptide receptor 2 (ALX/FPR2), RvE1 chemerin 23...
PrimPol is a human primase/polymerase specialized in downstream repriming of stalled forks during both nuclear and mitochondrial DNA replication. Like most primases polymerases, requires divalent metal cations, as Mg2+ or Mn2+, used cofactors for catalysis. However, little known about the consequences using these two combination, which would be physiological scenario PrimPol-mediated reactions, individual contribution putative carboxylate residues (Asp114, Glu116 Asp280) acting ligands. By...
G protein–coupled receptors (GPCRs) are biologic switches that transduce extracellular stimuli into intracellular responses in the cell. Temporally resolving GPCR transduction pathways is key to understanding how cell signaling occurs. Here, we investigate kinetics and dynamics of activation early steps CXC chemokine receptor (CXCR) 4 response its natural ligands ligand (CXCL) 12 macrophage migration inhibitory factor (MIF), using Förster resonance energy transfer–based approaches. We show...
The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor 4 (CXCR4), and both proteins play central role in modulation diverse cellular processes, including proliferation cell survival. While chronic myeloid leukemia (CML) CXCR4 downregulated, thereby promoting mobilization progenitor cells into blood, highly expressed breast cancer cells, favoring migratory capacity these cells. Recently, LIM SH3 domain 1 (LASP1) has been described as novel binding partner...
ABSTRACT Atypical chemokine receptor 3 (ACKR3), formerly referred to as CXCR7, is considered be an interesting drug target. In this study we report on the synthesis, pharmacological characterization and radiolabeling of VUF15485, a new ACKR3 small-molecule agonist, that will serve important tool β-arrestin-biased receptor. VUF15485 binds with nanomolar affinity (pIC 50 = 8.3) human ACKR3, measured in [ 125 I]CXCL12 competition binding experiments. Moreover, BRET-based β-arrestin2 recruitment...
The CXCL12 chemokine receptor CXCR4 belongs to the GPCR superfamily and is often overexpressed in cancer, being involved tumor progression metastasis. How signaling integrates with other relevant oncogenic transduction pathways role of regulatory mechanisms such contexts are not well-understood. Recent data indicate concurrent upregulation certain tumors CXCR4, EGF (EGFR), G protein-coupled kinase 2 (GRK2), a node functionally linked both types. We have investigated model system effect EGFR...
The CXC chemokine receptor 4 (CXCR4) and the atypical 3 (ACKR3) are seven transmembrane receptors that involved in numerous pathologies, including several types of cancers. Both bind same chemokine, CXCL12, leading to significantly different outcomes. While CXCR4 activation generally leads canonical GPCR signaling, involving Gi proteins β‐arrestins, ACKR3, which is predominantly found intracellular vesicles, has been shown signal via β‐arrestin‐dependent signaling pathways. Understanding...