| Project/Area Number |
11307009
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MORIMOTO Chikao The Institute of Medical Science The University of Tokyo, Professor, 医科学研究所, 教授 (30119028)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASAKI Hiroshi The Institute of Medical Science The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (80280957)
HOSONO Osamu The Institute of Medical Science The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (50190210)
TANAKA Hirotoshi The Institute of Medical Science The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (00171794)
WATANABE Sumiko The Institute of Medical Science The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (60240735)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥36,600,000 (Direct Cost: ¥36,600,000)
Fiscal Year 2000: ¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 1999: ¥26,300,000 (Direct Cost: ¥26,300,000)
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| Keywords | B cell progenitors cells / integrin α5β1 / Extracelluar signal-regulated kinase / p27(Kip1) / cyclin-dependent kinase / BM stromal cells / p27^<ldpl> / CD29 / VLA / インテグリン / Cas-L分子 / T細胞共刺激 / T細胞遊走 / チロシンリン酸化 |
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| Research Abstract |
Attachment to bone marrow(BM)stromal cells is crucial for the normal growth and development of B-cell progenitors(pro-B). However, the molecular mechanisms by which contact facilitates the proliferation of pro-B cells are not completely understood. This study was performed to investigate this interaction.
Attachment to both KM102 and normal BM stromal cells significantly promoted the growth of Reh cells. Pretreatment of Reh cells with anti-integrin beta1 or alpha5 monoclonal antibody(mAb), but not alpha4 or ICAM-1 mAb, abrogated this enhancement of proliferation. Furthermore, stroma attachment resulted in shortening of the G(1)phase of cell cycle, significant increases cdk2 activity, degradation of cdk inhibitor p27-GST protein, and decrease in levels of p27(Kip1)protein. In addition, solid-phase cross-linking of alpha5 via immobilized antibody also resulted in extracellular signal-regulated(ERK)-2 kinase phosphorylation, increase in cdk2 activity, decrease in levels of p27(Kip1)protein, and enhanced proliferation that was inhibited by treatment with PD98059, a specific ERK inhibitor.
Integrin alpha5beta1-mediated stroma contact promotes the proliferation of B-cell progenitors through the activation of ERK-2, which in tum modulates cell cycle regulation machinery including induction of cdk2 activity and degradation of p27(Kip1)and contributing to acceleration of the G(1)phase of cell cycle progression.
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