Igß ubiquitination activates PI3K signals required for endosomal sorting.
J Exp Med
; 214(12): 3775-3790, 2017 Dec 04.
Article
em En
| MEDLINE
| ID: mdl-29141870
ABSTRACT
A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC). Surprisingly, MIIC targeting is dispensable for T cell-dependent immunity. Rather, it is critical for activating endosomal toll-like receptors and antiviral humoral immunity. These findings demonstrate a novel mechanism of receptor endosomal signaling required for specific peripheral immune responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endossomos
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Transdução de Sinais
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Antígenos CD79
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Ubiquitinação
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Fosfatidilinositol 3-Quinase
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article