1997 Fiscal Year Annual Research Report

低分子量G蛋白質による細胞の増殖、運動の制御機構

Research Project

Project/Area Number	09254103
Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Hiroshima University
Principal Investigator	菊池章広島大学, 医学部, 教授 (10204827)
Co-Investigator(Kenkyū-buntansha)	金保安則東京工業大学, 生命理工学部, 助教授 (00214437) 大矢禎一東京大学, 大学院・理学系研究科, 助教授 (20183767) 東江昭夫東京大学, 大学院・理学系研究科, 教授 (90029249) 服部成介国立精神神経センター, 診断研究部, 室長 (50143508) 佐藤孝哉東京工業大学, 生命理工学部, 寄附講座教員 (20251655)
Keywords	細胞増殖 / 細胞運動 / 発がん / 転移 / 低分子量G蛋白質 / Ras / Rho
Research Abstract	低分子量G蛋白質の中でも発がん、転移に重要であるRasとRhoの活性化機構と作用機構について解析を行った。Rasはチロシンキナーゼ型受容体により活性化されるが、血球系細胞においてサイトカイン受容体のIL-3受容体とG蛋白質共役型のトロンビン受容体からのシグナルによりRasが活性化され、いずれの系においてもmSos1が関与し、その上流で異なるチロシンキナーゼが機能していることが明らかになった。IL-3は血球系細胞の増殖、生存維持においてJNK1を活性化するが、この際にRasが必要であった。また、新規のRas抑制因子であるGapm1は選択的スプライシングによりその活性が調節されている可能性を見い出した。インテグリンを標的蛋白質とするR-RasはRasの活性化因子であるRasGRFにより活性化され、またGapm1およびp120GAPにより機能が抑制された。Rasの標的蛋白質であるRalGDSはRafと相乗的に作用して、遺伝子発現を促進した。さらに、RalGDSにより活性化されるRalの標的蛋白質であるRalBP1と結合する新規蛋白質POB1を同定した。一方、Rhoは哺乳類細胞でも酵母でも細胞骨格を制御することが明らかになっているが、酵母Rho1が蛋白質リン酸化酵素Pkc1pと新規蛋白質Bni1pを介して、アクチン繊維の動態制御に関与し、さらにRho1pが酵母細胞壁の主要な構成成分である1,3-β-グルカンを合成する酵素の制御サブユニットとして働いた。また、酵母rho3の多コピー抑圧因子Sro9はトロポミオシンと共にアクチンの局在を制御し、Sro7はミオシンと結合した。ヒトRhoAは既に報告されているPLD活性化因子のARFと相乗的にPLDを活性化し、さらに、RhoAはPLDのC末端部分と直接結合した。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Murai,H.: "Characteriation of Ral GDP dissociation stimulator like(RGL)activities to regulate c-fos promoter and the GDP/GTP exchange of Ral." J.Biol.Chem.272・16. 10483-10490 (1997)
[Publications] Fukata,M.: "Regulation of cross-linking of actin filament by IQGAP1,a target for CDC42." J.Biol.Chem.272・47. 29579-29583 (1997)
[Publications] Okazaki,M.: "Synergistic activation of c-fos promoter activity by Ral GDP dissociation stimulator and Raf." Oncogene. 14・5. 515-521 (1997)
[Publications] Kishida,S.: "Colocalization of Ras and Ral on the membrane is required for Ras-dependent Ral activation through Ral GDP dissociation stimulator." Oncogene. 15・24. 2899-2907 (1997)
[Publications] Matsubara,K.: "The post-translational modifications of Ral and Rac are important for the action of Ral-binding protein 1,a putative effector protein of Ral." FEBS Lett.410・2,3. 169-174 (1997)
[Publications] Ikeda,M.: "Identification and Characterization of a novel protein which interacts with RalBP1,a putative effector protein of Ral." J.Biol.Chem.273・2. 814-821 (1998)
[Publications] Ikeda,S.: "Axin,a negative regulator of the Wnt signaling pathway,makes a complex with GSK-β and β-catenin and promotes GSK-3β-dependentβ-catenin phosphorylations." EMBO J.17・5. 1371-1384 (1998)
[Publications] Shirouzu,M.: "Interactions of the amino acid residues at position 31 on the c-Ha-Ras Protein with Raf-1 and RalGDS." J.Biol.Chem.(in press). (1998)
[Publications] Yamamoto,H.: "Axil,a member of Axin family,interacts both GSK-3β and β-catenin and inhibits axis formatio of Xenopus embryo." Mol.Cell.Biol.(in press). (1998)
[Publications] Kishida,S.: "Axin,a negative regulator of the Wnt signaling pathway pathway,directly interacts with APC and regulates the stabilization of β-catenin." J.Biol.Chem.(in press). (1998)
[Publications] Terada,K.: "Ras-dependent activation of c-Jun N-terminal kinase/stress-activated protein kinase in response to interleukin-3 stimulation in hematopoietic BaF3 cells." J.Biol.Chem.272・7. 4544-4548 (1997)
[Publications] Gotoh,T.: "Activation of R-Ras by Ras-guanine nucleotide-releasing factor." J.Biol.Chem.272・30. 18602-18607 (1997)
[Publications] Li,S.: "Activation of R-Ras GTPase by GTPase-activation proteins for Ras,Gap1m and p120 GAP." J.Biol.Chem.272・31. 19328-19332 (1997)
[Publications] Kominami,K.: "Yeast counterparts of subunits S5a and p58(S3)of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1." Mol.Biol.Cell.8・1. 171-187 (1997)
[Publications] Uesono,Y.: "Ssd1 of Saccharomyces cerevisiae associates with RNA." J.Biol.Chem.272・26. 16103-16109 (1997)
[Publications] Kawasaki,M.: "Identification of three core regions essential for protein splicing of the yeast Vma1 protopzyme." J.Biol.Chem.272・25. 15668-15674 (1997)
[Publications] Takita,Y.: "Applications of the long and accurate polymerase chain reaction method in yeast molecular biology : Direct sequencing of the amplified DNA and its introduction into yeast." Yeast. 13・8. 763-768 (1997)
[Publications] Tanaka,K.: "A target of phosphatidylinositol 3,4,5-trisphosphate with a Zinc finger motif similar to that of the ADP-ribosylation-factor GTPase-activating protein and two pleckstrin homology domains." Eur.J.Biochem.245・2. 512-519 (1997)

1997 Fiscal Year Annual Research Report

低分子量G蛋白質による細胞の増殖、運動の制御機構

Principal Investigator

菊池 章 広島大学, 医学部, 教授 (10204827)

Research Products

[Publications] Murai,H.: "Characteriation of Ral GDP dissociation stimulator like(RGL)activities to regulate c-fos promoter and the GDP/GTP exchange of Ral." J.Biol.Chem.272・16. 10483-10490 (1997)

[Publications] Fukata,M.: "Regulation of cross-linking of actin filament by IQGAP1,a target for CDC42." J.Biol.Chem.272・47. 29579-29583 (1997)

[Publications] Okazaki,M.: "Synergistic activation of c-fos promoter activity by Ral GDP dissociation stimulator and Raf." Oncogene. 14・5. 515-521 (1997)

[Publications] Kishida,S.: "Colocalization of Ras and Ral on the membrane is required for Ras-dependent Ral activation through Ral GDP dissociation stimulator." Oncogene. 15・24. 2899-2907 (1997)

[Publications] Matsubara,K.: "The post-translational modifications of Ral and Rac are important for the action of Ral-binding protein 1,a putative effector protein of Ral." FEBS Lett.410・2,3. 169-174 (1997)

[Publications] Ikeda,M.: "Identification and Characterization of a novel protein which interacts with RalBP1,a putative effector protein of Ral." J.Biol.Chem.273・2. 814-821 (1998)

[Publications] Ikeda,S.: "Axin,a negative regulator of the Wnt signaling pathway,makes a complex with GSK-β and β-catenin and promotes GSK-3β-dependentβ-catenin phosphorylations." EMBO J.17・5. 1371-1384 (1998)

[Publications] Shirouzu,M.: "Interactions of the amino acid residues at position 31 on the c-Ha-Ras Protein with Raf-1 and RalGDS." J.Biol.Chem.(in press). (1998)

[Publications] Yamamoto,H.: "Axil,a member of Axin family,interacts both GSK-3β and β-catenin and inhibits axis formatio of Xenopus embryo." Mol.Cell.Biol.(in press). (1998)

[Publications] Kishida,S.: "Axin,a negative regulator of the Wnt signaling pathway pathway,directly interacts with APC and regulates the stabilization of β-catenin." J.Biol.Chem.(in press). (1998)

[Publications] Terada,K.: "Ras-dependent activation of c-Jun N-terminal kinase/stress-activated protein kinase in response to interleukin-3 stimulation in hematopoietic BaF3 cells." J.Biol.Chem.272・7. 4544-4548 (1997)

[Publications] Gotoh,T.: "Activation of R-Ras by Ras-guanine nucleotide-releasing factor." J.Biol.Chem.272・30. 18602-18607 (1997)

[Publications] Li,S.: "Activation of R-Ras GTPase by GTPase-activation proteins for Ras,Gap1m and p120 GAP." J.Biol.Chem.272・31. 19328-19332 (1997)

[Publications] Kominami,K.: "Yeast counterparts of subunits S5a and p58(S3)of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1." Mol.Biol.Cell.8・1. 171-187 (1997)

[Publications] Uesono,Y.: "Ssd1 of Saccharomyces cerevisiae associates with RNA." J.Biol.Chem.272・26. 16103-16109 (1997)

[Publications] Kawasaki,M.: "Identification of three core regions essential for protein splicing of the yeast Vma1 protopzyme." J.Biol.Chem.272・25. 15668-15674 (1997)

[Publications] Takita,Y.: "Applications of the long and accurate polymerase chain reaction method in yeast molecular biology : Direct sequencing of the amplified DNA and its introduction into yeast." Yeast. 13・8. 763-768 (1997)

[Publications] Tanaka,K.: "A target of phosphatidylinositol 3,4,5-trisphosphate with a Zinc finger motif similar to that of the ADP-ribosylation-factor GTPase-activating protein and two pleckstrin homology domains." Eur.J.Biochem.245・2. 512-519 (1997)

菊池章広島大学, 医学部, 教授 (10204827)