2015 Fiscal Year Final Research Report
A study of cytokine signal transduction regulated by protein acetylation
| Project/Area Number |
25460600
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Toho University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KONDO Motonari 東邦大学, 医学部, 教授 (20594344)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | サイトカイン / シグナル伝達 / タンパク質修飾 |
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| Outline of Final Research Achievements |
Ligand binding to the cognate cytokine receptors activates intracellular signaling by recruiting protein tyrosine kinases and other protein modification enzymes. However, the roles of protein modifications other than phosphorylation remain unclear. Here, we examine a novel regulatory mechanism of Stat5 based on its acetylation. As for phosphorylation, interleukin 2 (IL-2) induces the acetylation of signaling molecules including Stat5 in the murine T cell line CTLL-2. Stat5 is acetylated in the cytoplasm by CREB-binding protein (CBP). Acetyl-Lys696 and -Lys700 on Stat5 are critical indicators for limited proteolysis, which leads to the generation of a truncated form of Stat5 (tStat5). In turn, tStat5 prevents transcription of the full-length form of Stat5. We also demonstrate that CBP physically associates with the IL-2 receptor β chain. CBP, found in the nucleus in resting CTLL-2 cells, relocates to the cytoplasm after IL-2 stimulation in a MEK/ERK pathway-dependent manner.
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| Free Research Field |
免疫学
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