Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation
| Autor: | Akira Matsumoto, Noriyasu Seki, Tadamitsu Kishimoto, Masato Kubo, J T Ransom, Akihiko Yoshimura, Jun Tsukada, Tetsuji Naka, Yoh Ichi Seki, Katsuhiko Hayashi |
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| Rok vydání: | 2002 |
| Předmět: |
Cytoplasm
Time Factors Transcription Genetic Recombinant Fusion Proteins Enzyme-Linked Immunosorbent Assay Suppressor of Cytokine Signaling Proteins Biology Suppressor of cytokine signalling Cell Line Mice Th2 Cells Animals SOCS5 Transgenes IL-2 receptor Phosphorylation Luciferases Promoter Regions Genetic Glutathione Transferase Multidisciplinary Dose-Response Relationship Drug Janus kinase 1 Suppressor of cytokine signaling 1 Proteins JAK-STAT signaling pathway Cell Differentiation Th1 Cells Biological Sciences Blotting Northern Interleukin-13 receptor Precipitin Tests Receptors Interleukin-4 Interleukin 15 Protein Biosynthesis Trans-Activators Cancer research Interleukin-4 STAT6 Transcription Factor Protein Binding Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 99:13003-13008 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.202477099 |
| Popis: | The development of helper T (Th) cell subsets, which secrete distinct cytokines, plays an important role in determining the type of immune response. The IL-4-mediated Janus kinase–signal transducer and activator of transcription signaling pathway is crucial for mediating Th2 cell development. Notably, this pathway is selectively impaired in Th1 cells, although the molecular basis of this impairment remains unclear. We show here that during Th1 differentiation a reduction in the association of Janus kinase 1 with the IL-4 receptor (IL-4R) correlated with the appearance of the suppressor of cytokine signaling-5 (SOCS5). SOCS5 protein was preferentially expressed in committed Th1 cells and interacted with the cytoplasmic region of the IL-4Rα chain irrespective of receptor tyrosine phosphorylation. This unconventional interaction of SOCS5 protein with the IL-4R resulted in the inhibition of IL-4-mediated signal transducer and activator of transcription-6 activation. T cells from transgenic mice constitutively expressing SOCS5 exhibited a significant reduction of IL-4-mediated Th2 development. Therefore, the induced SOCS5 protein in Th1 differentiation environment may play an important role by regulating Th1 and Th2 balance. |
| Databáze: | OpenAIRE |
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