Receptor oligomerization: A pivotal mechanism for regulating chemokine function
| Autor: | Mario Mellado, Rubén Barroso, Laura Martínez Muñoz, Borja L. Holgado, Pilar de Lucas, Beatriz Vega, José Miguel Rodríguez-Frade |
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| Jazyk: | angličtina |
| Předmět: |
Pharmacology
CCR1 0303 health sciences Protein Conformation Receptor expression C-C chemokine receptor type 7 C-C chemokine receptor type 6 Biology Cell biology 03 medical and health sciences Chemokine receptor 0302 clinical medicine Drug Design 030220 oncology & carcinogenesis Animals Receptors Chemokine Pharmacology (medical) CXC chemokine receptors Chemokines CCL25 Protein Binding 030304 developmental biology CCL21 |
| Popis: | Since the first reports on chemokine function, much information has been generated on the implications of these molecules in numerous physiological and pathological processes, as well as on the signaling events activated through their binding to receptors. Despite these extensive studies, no chemokine-related drugs have yet been approved for use in patients with inflammatory or autoimmune diseases. This discrepancy between efforts and results has forced a re-evaluation of the chemokine field. We have explored chemokine receptor conformations at the cell surface and found that, as is the case for other G protein-coupled receptors, chemokine receptors are not isolated entities that are activated following ligand binding; rather, they are found as dimers and/or higher order oligomers at the cell surface, even in the absence of ligands. These complexes form organized arrays that can be modified by receptor expression and ligand levels, indicating that they are dynamic structures. The way in which these receptor complexes are stabilized modulates ligand binding, as well as their pharmacological properties and the signaling events activated. These conformations thus represent a mechanism that increases the broad variety of chemokine functions. Understanding these receptor interactions and their dynamics at the cell surface is thus critical for influencing chemokine function and could open up new possibilities for drug design. |
| Databáze: | OpenAIRE |
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