Dok-1 regulates mast cell degranulation negatively through inhibiting calcium-dependent F-actin disassembly
Copyright © 2022. Published by Elsevier Inc.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 238(2022) vom: 02. Mai, Seite 109008 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2022
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Actin filament Ca(2+) Downstream of tyrosine kinase FcεRI Food allergy RBL-2H3 Actins Receptors, IgE mehr... |
| Zusammenfassung: | Copyright © 2022. Published by Elsevier Inc. In food allergies, antigen-induced aggregation of FcεRI on mast cells initiates highly ordered and sequential signaling events. Dok-1(downstream of tyrosine kinase 1), undergoes intense tyrosine phosphorylation upon FcεRI stimulation, which negatively regulates Ras/Erk signaling and the subsequent cytokine release, but it remains unclear whether Dok-1 regulates Fc-mediated degranulation. In this study, we investigated the role of Dok-1 in FcεRI-mediated degranulation. Dok-1 overexpressing RBL-2H3 cells were established. Degranulation, immunoprecipitation, co-immunoprecipitation, immunoblotting and flow cytometry assay were performed to explore the effects of Dok-1 and its underlying mechanisms. We found that, following FcεRI activation, Dok-1 was recruited to the plasma membrane, leading to tyrosine phosphorylation. Phosphorylated Dok-1 inhibits FcεRI-operated calcium influx, and negatively regulated degranulation by inhibiting calcium-dependent disassembly of actin filaments. Our data revealed that Dok-1 is a negative regulator of FcεRI-mediated mast cell degranulation. These findings contribute to the identification of therapeutic targets for food allergies |
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| Beschreibung: | Date Completed 17.05.2022 Date Revised 20.05.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2022.109008 |