1997 Fiscal Year Final Research Report Summary
Mechanisms of IL-6 function determining growth and differentiation of lymphocytes and marophages
Project/Area Number |
08457105
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
|
Research Institution | Osaka University |
Principal Investigator |
NAKAJIMA Koichi Osaka University Medical School, Associate Professor, 医学部, 助教授 (00227787)
|
Project Period (FY) |
1996 – 1997
|
Keywords | IL-6 / JAK / STAT / Ras / MAP kinase / Growth and Differentiation / stat3 gene / CDK inhibitor, p19^<INK4D> / IL-6 response element / gp130 |
Research Abstract |
1. We have elucidated the roles of each signaling pathways of IL-6 in a variety of cells using a series of gp130 mutant receptors and dominant-negative STA T3. The points made clear are as follows. 1) STA T3 activity is critical in IL-6-induced growth arrest and macrophage differentiation of M1 leukemic cells. STA T3 is involved in both repression of c-myc and c-myb expression and activation of junB and IRF1.2) For proliferative signals, both STA T3-mediated signals and another signals derived from the second tyrosine residue of gp130 are required in BAF/B03 cells. Especially, STA T3 provides anti-apoptotic signals. 3) In collaboration with us, Drs.Fukui and Ihara showed that Ras/MAP kinase pathway is critical in IL-6 induced neutrite outgrowth of PC12 cells which had been pretreated with NGF for 2h. Importantly, STA T3 has a negative effect on the neurite inducing activity. Consistently with this, NGF pretreatment was found to attenuate the subsequent STA T3 activation by IL-6. 2. We showed that the carboxi-terminal region of STA T5 can bind to the kinase-like domain of JAK kinases and presented a model, where JAK kinases activated by IL-6 directly phosphorylate and activate STA T5 without using phsophorylated tyrosine residues of the gp130. 3. We identified two other target genes for STA T3 in M1 cells. Both the p19^<INK4D> gene, a CDK inhibitor, and the stat3 gene itself are activated by STA T3. We further showed that STA T3 rapidly induced transcriptional activation of the stat3 gene through an IL-6 response element, located at -335/-314 in the stat3 gene promoter, which consists of a low-affinity STA T binding element and a CRE.Complex formation containing a STA T3 homo-dimer and an unidentified CRE-binding protein are required for full response. The autoregulatory loop is likely to be involved in the sustained activation of STA T3 observed in IL-6-stimulated M1 cells.
|
Research Products
(22 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Publications] Fujitani, Y., M.Hibi, T.Fukada, M.Takahashi-Tezuka, H.Yoshida, T.Yamaguchi, K.Sugiyama, Y.Yamanaka, K.Nakajima, and T.Hirano.: "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT." Oncogene. 14. 751-761 (1997)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Matsumura, I., J.Ishikawa, K.Nakajima, K.Oritani, Y.Tomiyama, J.Miyagawa, T.Kato, H.Miyazaki, Y.Matsuzawa, and Y.Kanakura: "Thrombopoietin-induced differentiation of a human megakaryoblastic leukemia cell line CMK involves transcriptional activation of p21WAF1/Cip1 by STA T5." Mol.Cell.Biol.17. 2933-2943 (1997)
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-