CD26 Mediates Dissociation of Tollip and IRAK-1 from Caveolin-1 and Induces Upregulation of CD86 on Antigen-Presenting Cells
| Autor: | Hirotoshi Tanaka, Osamu Hosono, Kunika Nishibashi, Satoshi Iwata, Kei Ohnuma, Nam H. Dang, Masahiko Uchiyama, Hiroshi Kawasaki, Tadanori Yamochi, Chikao Morimoto |
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| Rok vydání: | 2005 |
| Předmět: |
Dipeptidyl Peptidase 4
T-Lymphocytes Caveolin 1 Antigen-Presenting Cells Biology Caveolins Monocytes Cell Line Downregulation and upregulation Antigens CD Chlorocebus aethiops Tetanus Toxoid Animals Humans RNA Small Interfering Phosphotyrosine Promoter Regions Genetic Antigen-presenting cell Molecular Biology Cell Proliferation CD86 Membrane Glycoproteins TOLLIP Binding protein Cell Membrane Intracellular Signaling Peptides and Proteins Cell Biology Molecular biology Up-Regulation Cell biology Interleukin-1 Receptor-Associated Kinases Phosphorylation B7-2 Antigen Signal transduction Protein Kinases Protein Binding Signal Transduction |
| Zdroj: | Molecular and Cellular Biology. 25:7743-7757 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.25.17.7743-7757.2005 |
| Popis: | CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV enzyme activity in its extracellular region. We have previously reported that the addition of recombinant soluble CD26 resulted in enhanced proliferation of human T lymphocytes induced by the recall antigen tetanus toxoid (TT) via upregulation of CD86 on monocytes and that caveolin-1 was a binding protein of CD26, and the CD26-caveolin-1 interaction resulted in caveolin-1 phosphorylation (p-cav-1) as well as TT-mediated T-cell proliferation. However, the mechanism involved in this immune enhancement has not yet been elucidated. In the present work, we perform experiments to identify the molecular mechanisms by which p-cav-1 leads directly to the upregulation of CD86. Through proteomic analysis, we identify Tollip (Toll-interacting protein) and IRAK-1 (interleukin-1 receptor-associated serine/threonine kinase 1) as caveolin-1-interacting proteins in monocytes. We also demonstrate that following stimulation by exogenous CD26, Tollip and IRAK-1 dissociate from caveolin-1, and IRAK-1 is then phosphorylated in the cytosol, leading to the upregulation of CD86 via activation of NF-kappaB. Binding of CD26 to caveolin-1 therefore regulates signaling pathways in antigen-presenting cells to induce antigen-specific T-cell proliferation. |
| Databáze: | OpenAIRE |
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