Abnormal expressions of RasGRPs in autoimmune diseases
| Project/Area Number |
20591163
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Hokkaido University |
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Principal Investigator |
YASUDA Shinsuke Hokkaido University, 大学院・医学研究科, 助教 (00374231)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 自己免疫疾患 / 全身性エリテマトーデス / スプライス異常 / RasGRP1 / スプライスバリアント / 関節リウマチ / RasGRP4 |
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| Research Abstract |
Ras guanyl nucleotide-releasing proteins (RasGRPs) are guanine exchange factors for Ras. Among them, RasGRP1 is preferentially expressed in T cells. We have investigated abnormal expressions of RasGRP1 in patients with systemic lupus erythematosus and previously reported that alternative splicing of RasGRP1 is abundant in lupus T cells that alternative splicing is related to lower protein levels of this signaling molecule. In the present study, we at first tested if nonsense-mediated mRNA decay and/or ubiquitine-proteasome pathway play a role in lower protein levels of RasGRP1 in lupus T cells. Inhibition of nonsense-mediated mRNA decay nor proteasome impact the expression levels or patterns of RasGRP1 protein. Then we decided to generate Tg mice expressing RasGRP1 splice variant A, the most frequent alternatively-spliced RasGRP1 isoform, exclusively in T cells. We successfully generate mice that express RasGRP1 splice variant A protein in their thymus. Although proportion of single positive/double negative T cells in the thymus was not apparently affected by this splice variant, we are investigating activation of Ras-Erk pathway in Tg Tcells when stimulated by anti-CD3/28 antibodies.
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Report
(4 results)
Research Products
(55 results)
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[Journal Article] Increased expression of phospholipid scramblase 1 in monocytes from patients with systemic lupus erythematosus.2010
Author(s)
Suzuki E, Amengual O, Atsumi T, Oku K, Hashimoto T, Kataoka H, Horita T, Yasuda S, Ieko M, Fukushima K, Koike T
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Journal Title
J Rheumatol. 37(8)
Pages: 1639-45
Related Report
Peer Reviewed
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[Journal Article] The effects of phosphatidylserine-dependent antiprothrombin antibody on thrombin generation.2009
Author(s)
Sakai Y, Atsumi T, Ieko M, Amengual O, Furukawa S, Furusaki A, Bohgaki M, Kataoka H, Horita T, Yasuda S, Koike T
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Journal Title
Arthritis Rheum. 60(8)
Pages: 2457-67
Related Report
Peer Reviewed
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[Journal Article] Immunological reconstitution after autologous hematopoietic stem cell transplantation in patients with systemic sclerosis : relationship between clinical benefits and intensity of immunosuppression.2009
Author(s)
Bohgaki T, Atsumi T, Bohgaki M, Furusaki A, Kondo M, Sato-Matsumura KC, Abe R, Kataoka H, Horita T, Yasuda S, Amasaki Y, Nishio M, Sawada K, Shimizu H, Koike T
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Journal Title
J Rheumatol. 36(6)
Pages: 1240-8
Related Report
Peer Reviewed
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[Journal Article] Complement activation in patients with primary antiphospholipid syndrome.2009
Author(s)
Oku, K, Atsumi, T, Bohgaki, M, Amengual, O, Kataoka, H, Horita, T, Yasuda S, Koike T
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Journal Title
Ann Rheum Dis. 68(6)
Pages: 1030-5
Related Report
Peer Reviewed
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