A5035347866- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Advanced Biosensing Techniques and Applications
- Chemokine receptors and signaling
- Glycosylation and Glycoproteins Research
- Neuropeptides and Animal Physiology
- Immunotherapy and Immune Responses
- Chemical Synthesis and Analysis
- Neurobiology and Insect Physiology Research
- PI3K/AKT/mTOR signaling in cancer
- Diabetes Treatment and Management
Vrije Universiteit Amsterdam
2020-2024
University of Copenhagen
2022-2023
Amsterdam UMC Location Vrije Universiteit Amsterdam
2022
Background: The atypical chemokine receptor 3 (ACKR3) belongs to the superfamily of G protein-coupled receptors (GPCRs). Unlike classical GPCRs, this does not activate proteins in most cell types but recruits β-arrestins upon activation. ACKR3 plays an important role cancer and vascular diseases. As recruitment is triggered by phosphorylation C-terminal tail we studied different potential sites within C-tail further delineate molecular mechanism internalization trafficking GPCR. Methods: We...
The therapeutic potential of ligands targeting disease-associated membrane proteins is predicted by ligand-receptor binding constants, which can be determined using NanoLuciferase (NanoLuc)-based bioluminescence resonance energy transfer (NanoBRET) methods. However, the broad applicability these methods hampered restricted availability fluorescent probes. We describe use antibody fragments, like nanobodies, as universal building blocks for probes in NanoBRET. Our nanobody-NanoBRET (NanoB2)...
The 57-mer full-length GPR15L(25-81) peptide has been identified as the principal endogenous agonist of G protein-coupled receptor GPR15. Its main activity resides in C-terminal 11-mer GPR15L(71-81), which full efficacy but ~40-fold lower potency than peptide. Here, we systematically investigated structure-activity relationship GPR15L(71-81) by truncations/extensions, alanine-scanning, and N- capping. synthesized analogues were tested at GPR15 stably expressed HEK293A cells using a...
The chemokine receptor CXCR4 is overexpressed in many cancers and contributes to pathogenesis, disease progression, resistance therapies. known form oligomers, but the potential functional relevance malignancies remain elusive. Using a newly established nanobody-based BRET method, we demonstrate that oligomerization of endogenous on lymphoid cancer cell lines correlates with enhanced expression levels. Specific disruption oligomers reduced basal migration pro-survival signaling via changes...
Abstract The GPR15 receptor is a G protein‐coupled (GPCR), which activated by an endogenous peptide GPR15L(25–81) and C‐terminal fragment GPR15L(71–81). signals through the i/o pathway to decrease intracellular cyclic adenosine 3′,5′‐monophosphate (cAMP). However, activation profiles of within subtypes have not been examined. Moreover, whether can also couple s , q/11 12/13 unclear. Here, GPR15L(71–81) are used as pharmacological tool compounds delineate receptor‐mediated Gα protein...
Abstract Chemokine stimulation of atypical chemokine receptor 3 (ACKR3) does not activate G proteins but recruits arrestins. It is a scavenger that indirectly influences responses by restricting the availability CXCL12, an agonist shared with canonical CXCR4. ACKR3 upregulated in numerous disorders. Due to limited insights chemokine-activated signaling, it unclear how contributes pathological phenotypes. One explanation may be high constitutive activity drives non-canonical signaling through...
The therapeutic potential of ligands targeting disease-associated membrane proteins is predicted by ligand-receptor binding constants, which can be determined using NanoLuciferase (NanoLuc)-based Bioluminescence Resonance Energy Transfer (NanoBRET) methods. However, the broad applicability these methods hampered restricted availability fluorescent probes. We describe use antibody fragments, like nanobodies, as universal building blocks for probes in NanoBRET. Our nanobody-NanoBRET (NanoB2)...