| Project/Area Number |
04044054
|
|---|
| Research Category |
Grant-in-Aid for international Scientific Research
|
| Allocation Type | Single-year Grants |
|---|
| Section | Joint Research |
|---|
| Research Institution | THE UNIVERSITY OF TOKYO |
|---|
Principal Investigator |
ARAI Ken-ichi The University of Tokyo Professor THE INSTITUTE OF MEDICAL SCIENCE, 医科学研究所, 教授 (00012782)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
中川 菜峰子 (小谷野 菜) 東京大学, 医科学研究所, 教務職員
WATANABE Sumiko INSTITUTE OF MEDICAL SCIENCE,UNIV.OF TOKYO Research Associate, 医科学研究所, 教務職員 (60240735)
YOKOTA Takashi INSTITUTE OF MEDICAL SCIENCE,UNIV.OF TOKYO Associate Professor, 医科学研究所, 助教授 (50134622)
ARAI Naoko DNAX RESEARCH INSTITUTE Vice director & Senior Scientist, 副部長
JAN de Vries DNAX分子細胞生物学研究所, 部長
WOLFRAM Oste ハンブルグ大学, Heinrich Pette研究所, 教授
MIYAJIMA Atsushi DNAX RESEARCH INSTITUTE Vice director & Senior Scientist, 主任研究員
KOYANO Naoko (NAKAGAWA Na) INSITUTE OF MEDICAL SCIENCE,UNIV.OF TOKYO Research Associate
DEVRIES Jan DNAX RESEARCH INSTITUTE Director
OSTERTAG Walfram HEINRICH PETTE INST., HAMBRUG UNIV.Professor
DE Vries Jan DNAX分子細胞生物学研究所, 部長
OSTERTAG Wol ハンブルグ大学, Heinrich Pette研究所, 教授
DEVRIES Jan DNAX分子細胞生物学研究所, 部長
|
|---|
| Project Period (FY) |
1992 – 1994
|
| Project Status |
Completed (Fiscal Year 1994)
|
| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1993: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1992: ¥3,800,000 (Direct Cost: ¥3,800,000)
|
|---|
| Keywords | GM-CSF receptor / IL-3 receptor / Signal transduction / Transcription factor / Transactivator / Tyrosine phosphorylation / Gene transfer / Early response genes / トランスアクチベーター |
|---|
| Research Abstract |
1.Regulation of cytokine genes in T cells. Using human and mouse T cell clones with TH1, TH2, and TH0 phenotype, we have been working on the coordinate and differential expression of the IL-3, IL-4, IL-5 and GM-CSF genes. The CLE2/GC-box and CLE0 of the mouse GM-CSF promoter are essential for transcriptional activation in response to PMA and Ca ionophore. CLE2 defines a binding site for NF-kappaB.The major GC-box binding activity A1 was purified and was identified as Sp1. We purified a human NF-AT protein from activated Jurkat extract and showed that it strongly bound to the CLE0 within the GM-CSF promoter in association with AP1. We isolated a novel protein with zinc finger motifs which binds to the CT/GC-rich region of the IL-3 promoter. We also identified cis-regulatory elements within IL-5, IL-4 and IL-2 promoters. These works were done in collaboration with Drs.Naoko Arai and de Vries Jan in DNAX.
2.Receptor and Signal transduction. We have been working on the structure and function of GM-CSF/IL-3 receptors. There are several signal pathways downstream of the GM-CSF receptor. The membrane proximal region of betac is essential for proliferation, c-myc and pim-1 induction and Jak2 association. The C-terminal region of betac is important for the suppression of apoptosis, Ras, Raf, MAPK activation and c-fos, c-jun induction. We have also shown that bone marrow cells derived from transgenic mice which constitutively express hGM-CSF receptor have the proliferative capacity to induce all the myeloid cell lineages in response to hGM-CSF.Furthermore, we have generated mice carrying a null mutation of betac and betaIL-3. betac mutant mice also showed lung pathology consisting of lymphocytic infiltration and areas resembling alveolar proteinosis. These works were done in collaboration with Dr.Atsushi Miyajima in DNAX and Dr.Ostertag Wolfram in Hamburg University.
|
