In CD28-costimulated human naïve CD4+ T cells, I-κB kinase controls the expression of cell cycle regulatory proteins via interleukin-2-independent mechanisms
| Autor: | Lupino, Elisa, Buccinna', Barbara, Ramondetti, Cristina, Lomartire, Annarosa, DE MARCO, Giovanni, Ricotti, E, Tovo, Pier Angelo, Rinaudo, Maria Teresa, Piccinini, Marco |
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| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
CD28 CD3 Complex Pyridines Active Transport Cell Nucleus I-κB kinase inhibitors Gene Expression Cell Cycle Proteins I-κB kinase Lymphocyte Activation CD28 Antigens NF-KappaB Inhibitor alpha Quinoxalines Cyclin E CD4+ T cells cell cycle interleukin-2 CDC2-CDC28 Kinases Humans Cyclin D3 Protein Kinase Inhibitors S-Phase Kinase-Associated Proteins Cell Proliferation Oncogene Proteins Cell Cycle Cyclin-Dependent Kinase 2 Imidazoles Interleukin-2 Receptor alpha Subunit Intracellular Signaling Peptides and Proteins NF-kappa B Antibodies Monoclonal Original Articles Cyclin-Dependent Kinases I-kappa B Kinase Up-Regulation Gene Expression Regulation Interleukin-2 I-kappa B Proteins Carrier Proteins Heterocyclic Compounds 3-Ring Cyclin-Dependent Kinase Inhibitor p27 Signal Transduction |
| Zdroj: | Immunology. 131(2) |
| ISSN: | 1365-2567 |
| Popis: | Stimulation of naïve CD4(+) T cells through engagement of the T-cell receptor (TCR) and the CD28 co-receptor initiates cell proliferation which critically depends on interleukin (IL)-2 secretion and subsequent autocrine signalling via the IL-2 receptor. However, several studies indicate that in CD28-costimulated T cells additional IL-2-independent signals are also required for cell proliferation. In this study, using a neutralizing anti-human IL-2 antibody and two selective, structurally unrelated, cell-permeable I-κB kinase (IKK) inhibitors, BMS-345541 and PS-1145, we show that in human naïve CD4(+) T cells stimulated through a short engagement of the TCR and the CD28 co-receptor, IKK controls the expression of the cell cycle regulatory proteins cyclin D3, cyclin E and cyclin-dependent kinase 2 (CDK2) and the stability of the F-box protein S-phase kinase-associated protein 2 (SKP2) and its co-factor CDC28 protein kinase regulatory subunit 1B (CKS1B), through IL-2-independent mechanisms. |
| Databáze: | OpenAIRE |
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