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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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | サイトカイン / シグナル伝達 / タンパク質修飾 / サイトカイン情報伝達 / アセチル化 / 分子修飾 / タンパク質分子修飾 / リン酸化 / アセチル化修飾 |
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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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Report
(4 results)
Research Products
(18 results)
