Akt+ IKKα/β+ Rab5+ Signalosome Mediate the Endosomal Recruitment of Sec61 and Contribute to Cross-Presentation in Bone Marrow Precursor Cells
| Autor: | Nan Nan Lu, Xiang You, Chun Fang Hu, Dan Dan Xu, Feng Guang Gao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Endosome IKKα Immunology IKKβ lcsh:Medicine Article 03 medical and health sciences 0302 clinical medicine Antigen Drug Discovery Pharmacology (medical) Protein kinase B cross-presentation Pharmacology biology Kinase Chemistry Endoplasmic reticulum Akt lcsh:R Cross-presentation Sec61 Cell biology Ovalbumin 030104 developmental biology Infectious Diseases 030220 oncology & carcinogenesis biology.protein Phosphorylation bone marrow precursor cells |
| Zdroj: | Vaccines Vaccines, Vol 8, Iss 539, p 539 (2020) Volume 8 Issue 3 |
| ISSN: | 2076-393X |
| Popis: | Cross-presentation in dendritic cells (DC) requires the endosomal relocations of internalized antigens and the endoplasmic reticulum protein Sec61. Despite the fact that endotoxin-containing pathogen and endotoxin-free antigen have different effects on protein kinase B (Akt) and I-kappa B Kinase &alpha /&beta (IKK&alpha ) activation, the exact roles of Akt phosphorylation, IKK&alpha or IKK&beta activation in endotoxin-containing pathogen-derived cross-presentation are poorly understood. In this study, endotoxin-free ovalbumin supplemented with endotoxin was used as a model pathogen. We investigated the effects of endotoxin-containing pathogen and endotoxin-free antigen on Akt phosphorylation, IKK&alpha activation, and explored the mechanisms that the endotoxin-containing pathogen orchestrating the endosomal recruitment of Sec61 of the cross-presentation in bone marrow precursor cells (BMPC). We demonstrated that endotoxin-containing pathogen and endotoxin-free antigen efficiently induced the phosphorylation of Akt-IKK&alpha and Akt-IKK&alpha respectively. Endotoxin-containing pathogen derived Akt+ IKK&alpha + Rab5+ signalosome, together with augmented the recruitment of Sec61 toward endosome, lead to the increased cross-presentation in BMPC. Importantly, the endosomal recruitment of Sec61 was partly mediated by the formation of Akt+ IKK&alpha + signalosome. Thus, these data suggest that Akt+ IKK&alpha + Rab5+ signalosome contribute to endotoxin-containing pathogen-induced the endosomal recruitment of Sec61 and the superior efficacy of cross-presentation in BMPC. |
| Databáze: | OpenAIRE |
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