| Project/Area Number |
09357010
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
HIRAI Hisamaru Internal Medicine, University of Tokyo Hospital, Associate Professor, 医学部・附属病院, 助教授 (90181130)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HONDA Hiroaki Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (40245064)
CHIBA Shigeru Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (60212049)
MITANI Kinuko Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (50251244)
OGAWA Seishi Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (60292900)
SASAKI Ko Internal Medicine, University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 助手 (60282638)
|
|---|
| Project Period (FY) |
1997 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥28,500,000 (Direct Cost: ¥28,500,000)
Fiscal Year 1999: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1998: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 1997: ¥11,900,000 (Direct Cost: ¥11,900,000)
|
|---|
| Keywords | Notch / DSL domain / Jagged1 / differentiation / active Notch1 / transcription factor / GATA-2 / Notch1 / Notch2 / Notch3 / EGF様リピート / 造血幹細胞 / 自己複製能 / ストローマ細胞 / ES細胞 / 遺伝子治療 / CD34 / アデノウイルス / EGF受容体 / LTC-IC |
|---|
| Research Abstract |
The Delta/Serrate/LAG-2 (DSL) domain-containing proteins are considered to be ligands for Notch receptors. However, the physical interaction between DSL proteins and Notch receptors is poorly understood. We found that mJagged1 physically bound to mouse Notch2 (mNotch2) on the cell surface and to a purified extracellular portion of mNotch2, respectively, in a CaィイD22+-ィエD2dependent manner. Deletion mutant analyses showed that the DSL Domain of mJagged1 is a minimal binding unit and is indispensable for binding to mNotch2. The solid-phase binding assay showed that Jagged1 binds to Notch1 and Notch3 in addition to Notch2, suggesting that mJagged1 is a ligand for multiple Notch receptors. We further analyzed the expression levels of transcription factors, C/EBP α, C/EBPε, PU.1, AML1b, c-myb, and GATA-2 as myeloid-specific transcription factors, and SCL, GATA-1, GATA-2, NF-E2 (p45), MafK (p18), EKLF, and c-myb as erythroid-specific transcription factors, before and after stimulation for differentiation of the wild-type and aNotch1-expressing 32D myeloid cells and F5-5 erythroid cells, respectively. As a result, the expression levels of those transcription factors except GATA-2 showed the same pattern in the wild-type and aNotch1-expressing cells, whereas the expression level of GATA-2 was found unchanged after stimulation for differentiation in the aNotch1-expressing 32D cells but decreased in the wild-type cells, suggesting inhibition of differentiation by aNotch1 is mediated through GATA-2.
|
