1999 Fiscal Year Final Research Report Summary
Elucidation of the regulation mechanisms of the STAT3 signaling pathway in the immune cells
| Project/Area Number |
10470085
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Osaka City University |
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Principal Investigator |
NAKAJIMA Koichi Med.School, Prof., 医学部, 教授 (00227787)
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| Project Period (FY) |
1998 – 1999
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| Keywords | STAT3 / c-myc gene / IL-6 / gp130 / an H7-sensitive STAT3 kinase / pYXXQ motif / stat3 gene / knock-in mouse |
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| Research Abstract |
1. We have elucidated the roles of STAT3 in the gp 130-signal induced cell growth and c-myc gene activation. The points made clear are as follows. 1) STAT3 activity is critical in gp130-signal-induced cell growth and also in the G1 to S phase transition of BaF cells. STAT3 is involved in IL-6-induced c-myc activation both in HepG2 cells and in BaF cells. We found that STAT3 activates the c-myc gene promoter by directly binding to the region over-lapped with the E2F binding site in the c-myc gene promoter.
2. We characterized the STAT3 S727 kinase, which is sensitive to an inhibitor H7 and activated even by low doses of IL-6, and determined the gp130 region required for the kinase activation. We found that the pYXXQ motif was sufficient for S727 phosphorylation in an H7-sensitive manner. The pYXXQ-mediated pathway is distinct from Erk, p38 or PKCβ. We also showed that S727 phosphorylation is required for full transcriptional activity of STAT3. Thus the YXXQ motif has dual roles in regulating the STAT3 activity in concert ; one recruiting STAT3 to the receptor and the other activating an unidentified H7-sensitive STAT3 kinase pathway.
3. We made knock-in mice having point mutaions at the STAT binding site in the stat3 gene promoter at both alleles to investigate the role of auto-regulatoy loop in in vivo. The study is still on-going.
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[Publications] Kirito,K., Uchida,M,, Takatoku,M., Nakajima,K., Hirano,T., Miura,Y., and Komatsu,N.: "A novel function of stat1 and stat3 proteins in erythropoietin-induced erythroid differentiation of a human leukemia cell line"Blood. 92. 462-471 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tanaka H, I.Matsumura, K.Nakajima, H.Daino, J H.Sonoyama, H.Yoshida, K.Oritani, T.Machii, M.Yamamoto, M,T.Hirano, Y.Kanakura: "GATA-1 blocks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and bcl-2 in a murine myeloid cell line M1"Blood. 95(4). 1264-1273 (2000)
Description
「研究成果報告書概要(欧文)」より
