1997 年度実績報告書

細胞の増殖・分化のシグナル伝達機構

研究課題

研究課題/領域番号	06283221
研究種目	重点領域研究
研究機関	大阪大学
研究代表者	高井義美大阪大学, 医学部, 教授 (60093514)
研究分担者	佐々木卓也大阪大学, 医学部, 助手 (40241278) 田中一馬大阪大学, 医学部, 助教授 (60188290)
キーワード	低分子量GTP結合蛋白質 / Rho / Rab / アクチン細胞骨格 / 細胞内小胞輸送 / 細胞運動 / がん / 浸潤・転移
研究概要	RhoやRab低分子量GTP結合蛋白質を介するシグナル伝達経路の異常が、がん細胞の浸潤や転移に関与している可能性が出てきている。本年度の本研究において、私共は、RhoとRab低分子量GTP結合蛋白質の活性化機構と作用機構について解析を行い、以下の成果を得た。 (1)Rhoの活性化機構:アクチン繊維を細胞膜へAnchoringするERM(Ezrin,Radixin,Moesin)-CD44系のERMが、Rhoの活性制御蛋白質系(Rho GEPおよびRho GDI)と直接相互作用することにより、Rhoの活性化反応を開始することを明らかにした。 (2)Rhoの作用機構:Rhoが、その標的蛋白質であるBNI1に作用し、BNI1が、プロフィリンを介してアクチンの重合過程を、Elongation Factor 1α(EF1α)を介してアクチン繊維の再編成を制御することを明らかにした。さらに、Rho-BNI1系を細胞膜にAnchoringする蛋白質としてSPA2を単離した。 (3)Rho系とRab系の協調的作用:Rho系とRab系が、ストレスファイバーと接着班の消失および形成を協調的に制御することにより、細胞の運動を制御していることを明らかにした。 (4)Racの作用機構:Rhoファミリーに属するRacが、細胞間接着を制御する際に働くアクチン結合蛋白質として、Neurabin-IIを発見した。このように、私共は、本年度の研究予定をほぼ達成することができた。

研究成果

(32件)

すべてその他

すべて文献書誌 (32件)

[文献書誌] Wada,M.: "Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins." J.Biol.Chem.272・7. 3875-3878 (1997)
[文献書誌] Fukui,K.: "Isolation and characterization of a GTPase acstivating protein specific for the Rab3 subfamily of small G proteins." J.Biol.Chem.272・8. 4655-4658 (1997)
[文献書誌] Takeuchi,M.: "SAPAPs-A family of PSD-95/SAP90-associated proteins localized at postsynaptic density." J.Biol.Chem.272・18. 11943-11951 (1997)
[文献書誌] Horio,Y.: "Clustering and enhanced activity of an inwardly rectifying potassium channel,kir4.1,by an anchoring protein,PSD-95/SAP90." J.Biol.Chem.272・20. 12885-12888 (1997)
[文献書誌] Orita,S.: "Physical and functional interactions of Doc2 and Munc13 in Ca^<2+>-dependent exocytotic machinery." J.Biol.Chem.272・26. 16081-16084 (1997)
[文献書誌] Takahashi,K.: "Direct interaction of the Rho GDP dissociation inhibitor with Ezrin/Radixin/Moesin initiates the activation of the Rho small G protein." J.Biol.Chem.272・37. 23371-23375 (1997)
[文献書誌] Mandai,K.: "Afadin: A novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction." J.Cell Biol.139・2. 517-528 (1997)
[文献書誌] Nakanishi,H.: "Neurabin: A novel neural tissue-specific actin filament-binding protein involved in neurite formation." J.Cell Biol.139・4. 951-961 (1997)
[文献書誌] Takaishi,K.: "Requlation of cell-cell adhesion by Rac and Rho small G proteins in MDCK cells." J.Cell Biol.139・4. 1047-1059 (1997)
[文献書誌] Irie,M.: "Binding of neuroligins to PSD-95." Science. 277・5331. 1511-1515 (1997)
[文献書誌] Imamura,H.: "Bnilp and Bnrlp: downstream targets of the Rho family small G-proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae." ENBO J.16・10. 2745-2755 (1997)
[文献書誌] Kotani,H.: "Rho regulates association of both the ERM family and vinculin with the plasma membrane in MDCK cells." Oncogene. 14・14. 1705-1713 (1997)
[文献書誌] Koch,G.: "Association of the Rho family small GTP-binding proteins with Rho GDP dissociation inhibitor (Rho GDI)in Saccharomyces cerevisiae." Oncogene. 15・4. 417-422 (1997)
[文献書誌] Naito,A.: "Molecular cloning of mouse Doc2α and distribution of its mRNA in adult mouse brain." Mol.Brain Res.44・2. 198-204 (1997)
[文献書誌] Jin-no,Y.: "A novel function of the C-terminal lipid moieties of Rab3A small G protein implicated in Ca^<2+>-dependent exocytosis-Inhibition of interaction with GTP and reduction of this inhibition by phospholipid." Genes to Cells. 2・4. 273-288 (1997)
[文献書誌] Ohya,T.: "Involvement of Rabphilin3 in endocytosis through interaction with Rabaptin5." J.Biol.Chem.273・1. 613-617 (1998)
[文献書誌] Satoh,A.: "Neurabin-II/Spinophilin-An actin filament-binding protein with one PDZ domain localized at cadherin-based cell-cell adhesion sites." J.Biol.Chem.273・6. 3470-3475 (1998)
[文献書誌] Miki,H.: "Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP." Nature. 391・6662. 93-96 (1998)
[文献書誌] Asakura,T.: "Isolation and characterization of a novel actin filament-binding protein from Saccharomyces cerevisiae." Oncogene. 16・1. 121-130 (1998)
[文献書誌] Burns,M.E.: "Rabphilin-3A-A multifunctional regulator of synaptic vesicle traffic." J.Gen.Physiol.111・2. 243-255 (1998)
[文献書誌] Tanaka,K.: "Control of reorganization of the actin cytoskeleton by Rho family small GTP-binding proteins in yeast." Curr.Opin.Cell Biol.10・1. 112-116 (1998)
[文献書誌] Shimizu,K.: "Complex formation of SMAP/KAP3,a KIF3A/B ATPase Motor-associated protein,with a human chromosome-associated polypeptide." J.Biol.Chem.(in press). (1998)
[文献書誌] Fujita,Y.: "Tomosyn: A syntaxin-1-binding protein which forms a novel complex in the neurotransmitter release process." Neuron. (in press). (1998)
[文献書誌] Fujiwara,T.: "Rholp-Bnilp-Spa2p interactions-Implication in localization of Bnilp at the bud site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae." Mol.Biol.Cell. (in press). (1998)
[文献書誌] Umikawa,M.: "Interaction of Rholp target Bnilp and F-Actin-binding elongation factor lα-Implication in Rholp-regulated reorganization of the actin cytoskeleton in Saccharomyces cerevisiae." Oncogene. (in press). (1998)
[文献書誌] Takahashi,K.: "Interaction of Radixin with Rho small G protein GDP/GTP exchange protain Dbl." Oncogene. (in press). (1998)
[文献書誌] Mammoto,A.: "Interaction of drebrin and gephyrin with profilin." Biochem.Biophys.Res.Commun.(in press). (1998)
[文献書誌] Ide,N.: "Molecular cloning and characterization of rat lin-10." Blochem.Biophys.Res.Commun.(in press). (1998)
[文献書誌] Ide,N.: "Interaction of rat lin-10 with brain-enriched F-Actin-binding protein, neurabin-II/spinophilin." Biochem.Biophys.Res.Commun.(in press). (1998)
[文献書誌] Sasaki,T.: "The rho small G protein family-rho GDI system as a temporal and spatial determinant for cytoskeletal control." Biochem.Biophys.Res.Commun.(in press). (1998)
[文献書誌] Shimizu,K.et.al.: "Methods in Molecular Biology" Human Press Inc.,Totowa,NJ, 173-183 (1998)
[文献書誌] Orita,S. et.al.: "Frontiers of Neural Development" Springer-Verlag Tokyo Inc.,Tokyo (in press), (1998)

1997 年度 実績報告書

細胞の増殖・分化のシグナル伝達機構

研究代表者

高井 義美 大阪大学, 医学部, 教授 (60093514)

研究成果

[文献書誌] Wada,M.: "Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins." J.Biol.Chem.272・7. 3875-3878 (1997)

[文献書誌] Fukui,K.: "Isolation and characterization of a GTPase acstivating protein specific for the Rab3 subfamily of small G proteins." J.Biol.Chem.272・8. 4655-4658 (1997)

[文献書誌] Takeuchi,M.: "SAPAPs-A family of PSD-95/SAP90-associated proteins localized at postsynaptic density." J.Biol.Chem.272・18. 11943-11951 (1997)

[文献書誌] Horio,Y.: "Clustering and enhanced activity of an inwardly rectifying potassium channel,kir4.1,by an anchoring protein,PSD-95/SAP90." J.Biol.Chem.272・20. 12885-12888 (1997)

[文献書誌] Orita,S.: "Physical and functional interactions of Doc2 and Munc13 in Ca^<2+>-dependent exocytotic machinery." J.Biol.Chem.272・26. 16081-16084 (1997)

[文献書誌] Takahashi,K.: "Direct interaction of the Rho GDP dissociation inhibitor with Ezrin/Radixin/Moesin initiates the activation of the Rho small G protein." J.Biol.Chem.272・37. 23371-23375 (1997)

[文献書誌] Mandai,K.: "Afadin: A novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction." J.Cell Biol.139・2. 517-528 (1997)

[文献書誌] Nakanishi,H.: "Neurabin: A novel neural tissue-specific actin filament-binding protein involved in neurite formation." J.Cell Biol.139・4. 951-961 (1997)

[文献書誌] Takaishi,K.: "Requlation of cell-cell adhesion by Rac and Rho small G proteins in MDCK cells." J.Cell Biol.139・4. 1047-1059 (1997)

[文献書誌] Irie,M.: "Binding of neuroligins to PSD-95." Science. 277・5331. 1511-1515 (1997)

[文献書誌] Imamura,H.: "Bnilp and Bnrlp: downstream targets of the Rho family small G-proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae." ENBO J.16・10. 2745-2755 (1997)

[文献書誌] Kotani,H.: "Rho regulates association of both the ERM family and vinculin with the plasma membrane in MDCK cells." Oncogene. 14・14. 1705-1713 (1997)

[文献書誌] Koch,G.: "Association of the Rho family small GTP-binding proteins with Rho GDP dissociation inhibitor (Rho GDI)in Saccharomyces cerevisiae." Oncogene. 15・4. 417-422 (1997)

[文献書誌] Naito,A.: "Molecular cloning of mouse Doc2α and distribution of its mRNA in adult mouse brain." Mol.Brain Res.44・2. 198-204 (1997)

[文献書誌] Jin-no,Y.: "A novel function of the C-terminal lipid moieties of Rab3A small G protein implicated in Ca^<2+>-dependent exocytosis-Inhibition of interaction with GTP and reduction of this inhibition by phospholipid." Genes to Cells. 2・4. 273-288 (1997)

[文献書誌] Ohya,T.: "Involvement of Rabphilin3 in endocytosis through interaction with Rabaptin5." J.Biol.Chem.273・1. 613-617 (1998)

[文献書誌] Satoh,A.: "Neurabin-II/Spinophilin-An actin filament-binding protein with one PDZ domain localized at cadherin-based cell-cell adhesion sites." J.Biol.Chem.273・6. 3470-3475 (1998)

[文献書誌] Miki,H.: "Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP." Nature. 391・6662. 93-96 (1998)

[文献書誌] Asakura,T.: "Isolation and characterization of a novel actin filament-binding protein from Saccharomyces cerevisiae." Oncogene. 16・1. 121-130 (1998)

[文献書誌] Burns,M.E.: "Rabphilin-3A-A multifunctional regulator of synaptic vesicle traffic." J.Gen.Physiol.111・2. 243-255 (1998)

[文献書誌] Tanaka,K.: "Control of reorganization of the actin cytoskeleton by Rho family small GTP-binding proteins in yeast." Curr.Opin.Cell Biol.10・1. 112-116 (1998)

[文献書誌] Shimizu,K.: "Complex formation of SMAP/KAP3,a KIF3A/B ATPase Motor-associated protein,with a human chromosome-associated polypeptide." J.Biol.Chem.(in press). (1998)

[文献書誌] Fujita,Y.: "Tomosyn: A syntaxin-1-binding protein which forms a novel complex in the neurotransmitter release process." Neuron. (in press). (1998)

[文献書誌] Fujiwara,T.: "Rholp-Bnilp-Spa2p interactions-Implication in localization of Bnilp at the bud site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae." Mol.Biol.Cell. (in press). (1998)

[文献書誌] Umikawa,M.: "Interaction of Rholp target Bnilp and F-Actin-binding elongation factor lα-Implication in Rholp-regulated reorganization of the actin cytoskeleton in Saccharomyces cerevisiae." Oncogene. (in press). (1998)

[文献書誌] Takahashi,K.: "Interaction of Radixin with Rho small G protein GDP/GTP exchange protain Dbl." Oncogene. (in press). (1998)

[文献書誌] Mammoto,A.: "Interaction of drebrin and gephyrin with profilin." Biochem.Biophys.Res.Commun.(in press). (1998)

[文献書誌] Ide,N.: "Molecular cloning and characterization of rat lin-10." Blochem.Biophys.Res.Commun.(in press). (1998)

[文献書誌] Ide,N.: "Interaction of rat lin-10 with brain-enriched F-Actin-binding protein, neurabin-II/spinophilin." Biochem.Biophys.Res.Commun.(in press). (1998)

[文献書誌] Sasaki,T.: "The rho small G protein family-rho GDI system as a temporal and spatial determinant for cytoskeletal control." Biochem.Biophys.Res.Commun.(in press). (1998)

[文献書誌] Shimizu,K.et.al.: "Methods in Molecular Biology" Human Press Inc.,Totowa,NJ, 173-183 (1998)

[文献書誌] Orita,S. et.al.: "Frontiers of Neural Development" Springer-Verlag Tokyo Inc.,Tokyo (in press), (1998)

1997 年度実績報告書

高井義美大阪大学, 医学部, 教授 (60093514)