2004 Fiscal Year Final Research Report Summary
Mechanism of Regulation of Tyrosine Kinase Signaling
| Project/Area Number |
12219216
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyushu University (2001-2004)
Kurume University (2000) |
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Principal Investigator |
YOSHIMURA Akihiko Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (90182815)
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| Project Period (FY) |
2000 – 2004
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| Keywords | tyrosine kinase / STAT / SOCS / inflammation / tyrosine phsphorylation / hepatitis / hepayoma / interferon |
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| Research Abstract |
Most of growth factor receptors transmit signals through tyrosine kinases which is encoded in the intracellular domain, or non-covalently associated JAK kinases like cytokine receptors. Constitutive activation of tyrosine kinase is frequently associated with neoplasm and leukemic development ; for example Bcr-Abl for chronicmyelogenous leukemia. Furthermore, downstream moleculessuchas Ras and STATs play important roles in intracellular signal transduction as well as cancer development.
On the other hand, signal of cytokine plays important role on development of carcinogenesis and cancer through control of immune system as well as cell growth. About 20% of carcinoma has been thought to be derived from inflammation, however, there are many questions remained to be solved about inflammatory cytokines and their signals and carcinogenesis. Recently the TNF/NF-kB pathway has been implicated in inflammation-derived cancer, while we have investigated the STAT pathway, another important signal o
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f inflammatory cytokines. We have also investigated Ras/MAP kinase regulator Sprouty/Spred family proteins. Anti-tumor activity of SOCS1, a negative regulator of cytokine signaling, has been reported by many groups. SOCS1 may inhibit the development and/or progression of hepatocellular carcinoma, since SOCS1 expression is significantly reduced in HCC cells due to hyper-methylation of SOCS1 gene. In support of this, We have shown that SOCS1 heterozygous mice are hypersensitive to dimethylnitrosamine-induced hepatocarcinogenesis. In addition we have shown that reduction of SOCS1 expression is strongly associated with hepatitis and fibrosis. Thus, SOCS1 is a unique anti-oncogene that prevents inflammation-induced cancer. We also found that SOCS1 bound to oncogene product E7 of HPV, and induces degradation of E7, which results in the suppression of proliferation of cervical tumor cells, In addition, we found that Spred-1 interacts with not only Ras but also Rho and inhibits cell motility and metastasis of cancer cell. Less
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[Journal Article] Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness.2005
Author(s)
Inoue H, Kato R, Fukuyama S, Nonami A, Taniguchi K, Matsumoto K, Nakano T, Tsuda M, Matsumura M, Kubo M, lshikawa F, Moon BG, Takatsu K, Nakanishi Y, Yoshimura A.
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Journal Title
J Exp Med. 201
Pages: 73-82
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis2004
Author(s)
Yoshida T, Ogata H, Kamio M, Joo A, Shiraishi H, Tokunaga Y, Sata M, Nagai, H, Yoshimura, A.
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Journal Title
J Exp Med. 199
Pages: 1701-1707
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The Sprouty-related protein, Spred, inhibits cell motility, metastasis, and Rho-mediated actin reorganization.2004
Author(s)
Miyoshi K, Wakioka T, Nishinakamura H, Kamio M, Yang L, Inoue M, Hasegawa M, Yonemitsu Y, Komiya S, Yoshimura A.
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Journal Title
Oncogene. 23
Pages: 5567-5576
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages2003
Author(s)
Yasukawa H, Ohishi M, Mori H, Murakami M, Chinen T, Aki D, Hanada T, Takeda K, Akira S, Hoshijima M, Hirano T, Chien KR, Yoshimura A.
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Journal Title
Nature Immunol. 4
Pages: 551-556
Description
「研究成果報告書概要(欧文)」より
