Structure and function of memory T cell marker CD26
Structure and function of memory T cell marker CD26
批准号:
11694248
负责人:
MORIMOTO Chikao
金额:
$2.56万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B).
财政年份:
1999
资助国家:
日本
项目状态:
已结题
起止时间:
1999 至 2000
中文摘要
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英文摘要
CD26 is a T cell activation antigen known to bind adenosine deaminase and have dipeptidyl peptidase IV activity. Cross-linking of CD26 and CD3 with immobilized mAbs can deliver a costimulatory signal that contributes to T cell activation. Our earlier studies revealed that cross-linking of CD26 induces its internalization, the phosphorylation of a number of proteins involved in the signaling pathway, and subsequent T cell proliferation. Although these findings suggest the importance of internalization in the function of CD26, CD26 has only 6 aa residues in its cytoplasmic region with no known motif for endocytosis. In the present study, we have identified the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIR) as a binding protein for CD26 and that mannose 6-phosphate (M6P) residues in the carbohydrate moiety of CD26 are critical for this binding. Activation of peripheral blood T cells results in the mannose 6 phosphorylation of CD26. In addition, the cross-linking of CD26 with an anti-CD26 antibody induces not only capping and internalization of CD26 but also colocalization of CD26 with M6P/IGFIIR.Finally, both internalization of CD26 and the T cell proliferative response induced by CD26-mediated costimulation were inhibited by the addition of M6P, but not by glucose 6-phosphate or mannose 1-phosphate. These results indicate that internalization of CD26 after cross-linking is mediated in part by M6P/IGFIIR and that the interaction between mannose 6-phosphorylated CD26 and M6P/IGFIIR may play an important role in CD26-mediated T cell costimulatory signaling.
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Iwata S,and Morimoto C.: "CD26/Dipeptidyl peptidase IV in context : The different roles of a multifunctional ectoenzyme in malignant transformation"J.Exp.Med.. 190. 305 (301)
Iwata S 和 Morimoto C.:“背景中的 CD26/二肽基肽酶 IV:多功能胞外酶在恶性转化中的不同作用”J.Exp.Med.. 190. 305 (301)
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Iwata S,Ohashi Y,Kamiguchi K,Morimoto C: "Beta 1-integrin-mediated cell signaling in T lymphocytes"J Dermatol Sci. 23. 75-86 (2000)
Iwata S、Ohashi Y、Kamiguchi K、Morimoto C:“T 淋巴细胞中 Beta 1-整合素介导的细胞信号传导”J Dermatol Sci。
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Homma T,Hosono O,Iwata S,Ando S,Sasaki K,Nishi T,Kawasaki H,Tanaka H,Moromoto C: "Recognition of cell surface GD3 by monoclonal antibody anti-6C2 in rheumatoid arthiritis synovial fluid"Arthr.& Rheum. (in press).
Homma T、Hosono O、Iwata S、Ando S、Sasaki K、Nishi T、Kawasaki H、Tanaka H、Moromoto C:“类风湿关节炎滑液中抗 6C2 单克隆抗体对细胞表面 GD3 的识别”Arthr。
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Ikushima H,Munakata Y,Ishii T,Iwata S,Terashima M,Tanaka H,Schlossman SF,Morimoto C: "Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor I receptor contributes to T cell activation"Proc.Natl.Acad.Sci. 97. 8439-8444 (2000)
Ikushima H、Munakata Y、Ishii T、Iwata S、Terashima M、Tanaka H、Schlossman SF、Morimoto C:“甘露糖 6-磷酸/胰岛素样生长因子 I 受体对 CD26 的内化有助于 T 细胞激活”Proc.Natl
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Ohtsuki T, Tsuda H, Morimoto C: "Good or evil : CD26 and HIV infection."J Dermatol Sci.. 22. 152-60 (2000)
Ohtsuki T、Tsuda H、Morimoto C:“善还是恶:CD26 和 HIV 感染。”J Dermatol Sci.. 22. 152-60 (2000)
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共 16 条
Association of deubiquitin ligase and cell surface molecules regulates the pathophysiology of malignant pleural mesothelioma
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批准号:24659401
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项目类别:Grant-in-Aid for Challenging Exploratory Research
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资助金额:$2.33万
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财政年份:2012
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负责人:MORIMOTO Chikao
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依托单位:
To determine the epigenetic regulatory mechanism of cancer stem cells by cell surface molecules.
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批准号:22650223
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项目类别:Grant-in-Aid for Challenging Exploratory Research
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资助金额:$2.12万
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财政年份:2010
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负责人:MORIMOTO Chikao
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依托单位:
Basic research of defining the function of CD26 on human immune system and its clinical application for autoimmune diseases.
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批准号:22390200
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$11.98万
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财政年份:2010
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负责人:MORIMOTO Chikao
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依托单位:
Basic Approach for the Development of Molecular Target Therapy for Autoimmune Diseases and Immune-Mediated Disorders.
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批准号:17109011
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项目类别:Grant-in-Aid for Scientific Research (S)
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资助金额:$71.72万
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财政年份:2005
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负责人:MORIMOTO Chikao
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依托单位:
Basic study of molecular target therapy for autoimmune diseases and immune deficiency diseases based on CD26
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批准号:15209033
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项目类别:Grant-in-Aid for Scientific Research (A)
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资助金额:$26.79万
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财政年份:2003
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负责人:MORIMOTO Chikao
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依托单位:
The development of specific immune regulatory drugs utilizing the structure and function of CD26
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批准号:13557039
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$10.75万
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财政年份:2001
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负责人:MORIMOTO Chikao
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依托单位:
Analysis of the function of lymphocyte adhesion molecules and its clinical significances in autoimmune diseases
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批准号:13470107
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$10.43万
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财政年份:2001
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负责人:MORIMOTO Chikao
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依托单位:
Analysis of CD29/VLA integrin in T cell immune regulation and its clinical significance
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批准号:11307009
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项目类别:Grant-in-Aid for Scientific Research (A).
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资助金额:$23.42万
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财政年份:1999
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负责人:MORIMOTO Chikao
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依托单位:
Development of specific imuune regulatoly drugs by the cell surface molecules.
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批准号:10557049
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$8.06万
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财政年份:1998
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负责人:MORIMOTO Chikao
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依托单位:
Analysis of CD26 mediated signal transduction mechanism.
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批准号:09044266
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项目类别:Grant-in-Aid for international Scientific Research
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资助金额:$2.56万
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财政年份:1997
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负责人:MORIMOTO Chikao
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依托单位:
Determination of molecular basis of immunoregulation of human T cell circuit and its clinical significances
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批准号:09307009
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项目类别:Grant-in-Aid for Scientific Research (A)
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资助金额:$21.57万
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财政年份:1997
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负责人:MORIMOTO Chikao
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依托单位:
Development of immunoregulatory therapy via CD26 activation pathway.
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批准号:08557036
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项目类别:Grant-in-Aid for Scientific Research (A)
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资助金额:$10.18万
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财政年份:1996
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负责人:MORIMOTO Chikao
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依托单位:
海外基金