2012 Fiscal Year Final Research Report
Function of novel molecule Gasp exclusively expressed in the thymus
| Project/Area Number |
22390098
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
SUZUKI Harumi 独立行政法人国立国際医療研究センター, 免疫病理部, 部長 (70235985)
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| Co-Investigator(Kenkyū-buntansha) |
HAYAKAWA Kunihiro 国立国際医療研究センター, 免疫病理, 研究員 (00573007)
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| Project Period (FY) |
2010 – 2012
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| Keywords | リンパ球 / 胸腺 / T細胞 |
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| Research Abstract |
We identified a novel gene Gasp (Themis), which is exclusively expressed in the thymus and reported that Themis is critical in positive selection of thymocytes. Themis is a unique molecule that is absolutely required for positive selection, but is not required for negative selection and homeostatic expansion. Themis constitutively associates with Grb2 and tyrosine phosphorylated upon TCR-stimulation, therefore likely to be involved in TCR-dependent signal transduction. It is also involved in TCR-dependent IL-2 production, however, we could not observe any sign of modulating signaling strength. From domains deletion analysis of Themis, two of CABIT domains, a proline rich sequence (PRS), and a nuclear localization signal (NLS) are all shown to be required for its function. Collectively, Themis is not simply modulating strength of signal, but may be important for sustaining weak signal required for positive selection in the thymus. Molecular mechanism of Themis is still not well known, however, the current study unveiled its importance for IL-2 production, and differential function of the two CABIT domains. Themis may not simply modulate signaling strength like other signal transducers, but it may involved in spatiotemporal regulation of intracellular signal transduction.
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Research Products
(23 results)
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[Journal Article] Induction of CCAAT/enhancer-binding protein-homologous protein by cigarette smoke through the superoxide anion-triggered PERK-eIF2a pathway2011
Author(s)
Tagawa Y, Hiramatsu N, Kato H, Sakoh T, Nakajima S, Hayakawa K, Saito Y, Johno H, Takahashi S, Gu L, Yao J, Kitamura M
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Journal Title
Toxicology
Volume: 287
Pages: 105-112
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[Presentation] Overexpression of Gasp (Themis) augmented positive selection of thymocytes2011
Author(s)
Okada, T., Patrick M. S., Yoshimoto, T., Kaji, K., Tamehiro, N., Okamura, T., Suzuki, H.
Organizer
6^<th> Leukocyte Signal Transduction Workshop
Place of Presentation
Crete, Greek
Year and Date
20110600
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[Presentation] Effect of Gasp (Themis) on T cell development and TCR signaling2011
Author(s)
Okada, T., Patrick M. S., Yoshimoto, T., Kaji, K., Tamehiro, N., Okamura, T., Suzuki, H.
Organizer
EUThyme 2011
Place of Presentation
Amsterdam, Netherland
Year and Date
20110500
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