Dok-1 regulates mast cell degranulation negatively through inhibiting calcium-dependent F-actin disassembly

Copyright © 2022. Published by Elsevier Inc.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 238(2022) vom: 02. Mai, Seite 109008
1. Verfasser: Du, Hang (VerfasserIn)
Weitere Verfasser: Sun, Na, Han, Shiwen, Song, Ruolin, Che, Huilian
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
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... Tyrosine 42HK56048U Calcium SY7Q814VUP
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520 |a 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 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Actin filament 
650 4 |a Ca(2+) 
650 4 |a Downstream of tyrosine kinase 
650 4 |a FcεRI 
650 4 |a Food allergy 
650 4 |a RBL-2H3 
650 7 |a Actins  |2 NLM 
650 7 |a Receptors, IgE  |2 NLM 
650 7 |a Tyrosine  |2 NLM 
650 7 |a 42HK56048U  |2 NLM 
650 7 |a Calcium  |2 NLM 
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700 1 |a Sun, Na  |e verfasserin  |4 aut 
700 1 |a Han, Shiwen  |e verfasserin  |4 aut 
700 1 |a Song, Ruolin  |e verfasserin  |4 aut 
700 1 |a Che, Huilian  |e verfasserin  |4 aut 
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856 4 0 |u http://dx.doi.org/10.1016/j.clim.2022.109008  |3 Volltext 
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