1998 Fiscal Year Final Research Report Summary
Signainrg Mechanism and Biological Action of the Members of the Transforming Growh Factor beta Superfamily
| Project/Area Number |
09480199
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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 |
Cell biology
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
MIYAZONO Kohei The Cancer lhstitute, Department of Biochemisty, Chief, 癌研究所・生化学部, 部長 (90209908)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDOU Yasuhiro The Cancer Institute, Dept.Biochemistry, Researcher, 癌研究所・生化学部, 研究員 (10300740)
HANAI Jun-ichi The Cancer Institute, Dept.Biochemistry, Researcher, 癌研究所・生化学部, 研究員 (70261964)
IMAMURA Takeshi The Cancer Institute, Dept.Biochemistry, Researcher, 癌研究所・生化学部, 研究員 (70264421)
KATO Mitsuyasu The Cancer lhstitute, Dept. Biochemisty, Researcher, 癌研究所・生化学部, 研究員 (20194855)
KAWABATA Masahiro The Cancer Institute, Dept. Biochemistry, Associate Member, 癌研究所・生化学部, 主任研究員 (60224838)
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| Project Period (FY) |
1997 – 1998
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| Keywords | TGF-beta / BMP / tumor suppressor gene / signal transduction / growth inhibition / Smad / serine / threonine kinase / gene targeting |
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| Research Abstract |
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates the growth and differentiation of various cell types.TGF-beta binds to type I and type II serine/threonine kinase receptors, and activates Smad family of intracellular proteins.
(1) We investigated the interacting protein(s) with a serine/threonine kinase receptor in Drosophila (Thick veins) by yeast two-hybrid system.We isolated Drosophila inhibitor of apoptosis (DLAP)-1, which appeared to be involved in the signal transduction of TGF-beta family members.
(2) We have classified Smads into three subgroups, R-Smads, Co-Smads, and Anti-Smads.Smad6 isolated in this study turned out to be an Anti-Smad.
(3) Smad1 and Smad5, which transduce signals for BMPs, were infected into osteoprogenitor cells by an adenovirus system.Smad1/5 induced differentiation into osteoblasts in these cells, which was dramatically enhanced by the presence of ligands or active forms of receptors.
(4) A Smad3 mutant (Asp407 to Glu) acted as a dominant negative mutant.Human keratinocytes expressing a high level of the mutant was resistant to the growth inhibitory activity of TGF-beta.The cells also acquired an invasive phenotype in an in vitro culture system.
(5) Gene targeting of BMP type II receptor and Smad2 was done.Both knockout mice were embryonic lethal.
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[Publications] Imamura T., Takase, M., Nishihara, A., Oeda E., Hanai, J.-i., Kawabata, M.and Miyazono, K.: "Smad6 inhibits signalling by the TGF-beta superfamily." Nature. 389(6651). 622-626 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nakao, A., Imamura, T., Souchelnytskyi, S., Kawabata, M., Ishisaki, A., Oeda, E., Tamaki, K., Hanai, J.-i., Heldin, C.-H., Miyazono, K., and ten Dijke, P.: "TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4." EMBO J.16(17). 5353-5362 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Yagi, K., Goto, D, Hamamoto, T., Takenoshita, S., Kato, M.and Miyazono, K.: "Alternatively-spliced variant of Smad2 lacking exon 3 : Comparison with wild-type Smad2 and Smad3." J.Biol.Chem.274(2). 703-709 (1999)
Description
「研究成果報告書概要(欧文)」より
