2000 Fiscal Year Annual Research Report

細胞増殖のシグナリング機構

Research Project

Project/Area Number	12215079
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (C)
Research Institution	Osaka University
Principal Investigator	高井義美大阪大学, 医学系研究科, 教授 (60093514)
Co-Investigator(Kenkyū-buntansha)	萬代研二大阪大学, 医学系研究科, 助手 (50322186) 中西宏之大阪大学, 医学系研究科, 助教授 (80314318) 的崎尚大阪大学, 医学系研究科, 助教授 (80252782) 佐々木卓也徳島大学, 医学部, 教授 (40241278)
Keywords	細胞増殖 / 細胞接着 / 細胞運動 / Nectin-Afadin-Ponsin系 / Frabin-Cdc42系 / Cadherin-Catenin系 / Gab-1 / Rab11
Research Abstract	細胞接着のシグナル系は細胞の増殖や運動のシグナル系とクロストークし、これらシグナル系の異常は細胞のがん化やがん細胞の浸潤・転移と密接に関連している。これまで私共は、新しい細胞間接着機構であるNectin-Afadin-Ponsin(NAP)系と、新しい細胞運動の制御機構であるFrabin-Cdc42系を見出している。NAP系はCadherin-Catenin系と関連しながら、細胞間接着の形成を制御している。Frabinは、F-アクチン結合蛋白質であり、かつCdc42低分子量G蛋白質の特異的活性化因子である。そこで、本年度の本研究では、NAP系とFrabin-Cdc42系を中心に、細胞の増殖、接着、運動のシグナル系について解析を行い、以下の成果を得た。 (1)NAP系の作用機構:私共は、NAP系がα-Cateninとタイトジャンクションの構成分子ZO-1と連結し、Cadherin-Catenin系とZO-1を細胞間接着にリクルートすることを明らかにした。 (2)Frabin-Cdc42系の作用機構:Frabinは、その直接的なアクチン細胞骨格への作用とCdc42活性化作用が協調的に機能することによって、細胞運動を制御しているを見出した。 (3)細胞の増殖と接着のシグナル系のクロストーク:Cadherinによる細胞接着が、Srcファミリーを介してGab-1のチロシンリン酸化を引き起こし、MAPキナーゼとAktキナーゼを制御していることを明らかにした。 (4)Rabの作用機構:Rab11の標的蛋白質Rabphilin-11に結合する蛋白質として、酵母Sec13pの哺乳類ホモログであるmSec13pを同定し、Rab11-Rabphilin-11系がmSec13pとの相互作用を介して細胞運動を制御していることを明らかにした。このように、本年度の本研究は予想以上に進展し、当初の目的を達成することができた。

Research Products

(22 results)

All Other

All Publications (22 results)

[Publications] Miyahara,M.: "Interaction of nectin with afadin is necessary for its clustering at cell-cell contact sites but not for its cis dimerization or trans interaction."J.Biol.Chem.. 275・1. 613-618 (2000)
[Publications] Satoh-Horikawa,K.: "Nectin-3 : A new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities."J.Biol.Chem.. 275・14. 10291-10299 (2000)
[Publications] Mammoto,A.: "Physical and functional interaction of rabphilin-11 with mammalian sec13 protein.Implication in vesicle trafficking."J.Biol.Chem.. 275・18. 13167-13170 (2000)
[Publications] Deguchi,M.: "PAPAIN-A novel multiple PSD-95/Dlg-A/zO-1 protein interacting with neural plakophihlin-related armadillo-repeat protein(NPRAP)/ δ-catenin and p0071."J.Biol.Chem.. 275・38. 29875-29880 (2000)
[Publications] Tachibana,K.: "Two cell adhesion molecules, Nectin and Cadherin, interact through their cytoplasmic domain-associated proteins."J.Cell Biol.. 150・5. 1161-1176 (2000)
[Publications] Takakura,A.: "Involvement of a small GTP-binding protein (G protein) regulator, small G protein GDP dissociation stimulator, in antiapoptotic cell survival signaling."Mol.Biol.Cell. 11・5. 1875-1886 (2000)
[Publications] Kodama,A.: "Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth factor/scatter factor-induced cell scattering."Mol.Biol.Cell. 11・8. 2565-2575 (2000)
[Publications] Ono,Y.: "Two actions of frabin : direct activation of Cdc42 and indirect activation of Rac."Oncogene. 19・27. 3050-3058 (2000)
[Publications] Kikyo,M.: "Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2δ, an immunoglobulin-like cell adhesion molecule at adherens junctions."Oncogene. 19・35. 4022-4028 (2000)
[Publications] Yao,I.: "Association of membrane-associated guanylate kinase-interacting protein (MAGUIN)-1 with Raf-1."Biochem.Biophys.Res.Commun.. 270・2. 538-542 (2000)
[Publications] Fujiwara,T.: "Rho small G protein-dependent binding of mDia to a Src homology 3 domain-containing IRSp 53/BAIAP2 ."Biochem.Biophys.Res.Commun.. 271・3. 626-629 (2000)
[Publications] Takaishi,K.: "Mechanisms of activation and action of mDial in the formation of parallel stress fibers in MDCK cells."Biochem.Biophys.Res.Commun.. 274・1. 68-72 (2000)
[Publications] Yasuda,T.: "Importance of spatial activation of Cdc42 small G proteins by frabin for its functions in MDCK cells."Genes Cells. 5・7. 583-591 (2000)
[Publications] Takaishi,K.: "Multiple downstream signaling rathways from ROCK, a target molecule of Rho small G protein, in reorganization of the actin cytoskeleton in Madin-Darby canine kidney cells."Genes Cells. 5・11. 929-936 (2000)
[Publications] Peng,Y.F.: "Ankycorbin : A novel actin cytoskeleton-associated protein."Genes Cells. 5・12. 925-932 (2000)
[Publications] Mino,A.: "Membrane-associated guanylate kinase with inverted orientation(HAGI)-1/brain angiogenesis inhibitor 1-associated protein(BAP1) as a scaffolding molecule for Rap small G protein GDP/GTP exchange protein at tight junctions"Genes Cells. 5・12. 1009-1016 (2000)
[Publications] Suzuki,T.: "Rho family GTPase Cdc42 is essential for the actin-based motility of Shigella in mammalian cells."J.Exp.Med.. 191・11. 1905-1920 (2000)
[Publications] Mammoto A.: "Stimulation of Rho GDI relaease by ERM proteins."Methods Enzymol.. 325. 91-101 (2000)
[Publications] Matozaki,T.: "Small G protein networks : Their crosstalks and signal cascades."Cellular Signalling. 12・8. 515-524 (2000)
[Publications] Ozaki-Kuroda,K.: "Dynamic localization and function of Bnilp at the sites of directed growth in yeast Saccharomyces cerevisiae."Mol.Cell.Biol.. 21・3. 827-839 (2001)
[Publications] Takai,Y.: "Small GTP-binding proteins."Physiol.Rev.. 81・1. 153-208 (2001)
[Publications] Sakisaka,T.: "Requirement of interaction of Nectin-1α/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1."J.Virol.. (in press). (2001)

2000 Fiscal Year Annual Research Report

細胞増殖のシグナリング機構

Principal Investigator

高井 義美 大阪大学, 医学系研究科, 教授 (60093514)

Research Products

[Publications] Miyahara,M.: "Interaction of nectin with afadin is necessary for its clustering at cell-cell contact sites but not for its cis dimerization or trans interaction."J.Biol.Chem.. 275・1. 613-618 (2000)

[Publications] Satoh-Horikawa,K.: "Nectin-3 : A new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities."J.Biol.Chem.. 275・14. 10291-10299 (2000)

[Publications] Mammoto,A.: "Physical and functional interaction of rabphilin-11 with mammalian sec13 protein.Implication in vesicle trafficking."J.Biol.Chem.. 275・18. 13167-13170 (2000)

[Publications] Deguchi,M.: "PAPAIN-A novel multiple PSD-95/Dlg-A/zO-1 protein interacting with neural plakophihlin-related armadillo-repeat protein(NPRAP)/ δ-catenin and p0071."J.Biol.Chem.. 275・38. 29875-29880 (2000)

[Publications] Tachibana,K.: "Two cell adhesion molecules, Nectin and Cadherin, interact through their cytoplasmic domain-associated proteins."J.Cell Biol.. 150・5. 1161-1176 (2000)

[Publications] Takakura,A.: "Involvement of a small GTP-binding protein (G protein) regulator, small G protein GDP dissociation stimulator, in antiapoptotic cell survival signaling."Mol.Biol.Cell. 11・5. 1875-1886 (2000)

[Publications] Kodama,A.: "Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth factor/scatter factor-induced cell scattering."Mol.Biol.Cell. 11・8. 2565-2575 (2000)

[Publications] Ono,Y.: "Two actions of frabin : direct activation of Cdc42 and indirect activation of Rac."Oncogene. 19・27. 3050-3058 (2000)

[Publications] Kikyo,M.: "Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2δ, an immunoglobulin-like cell adhesion molecule at adherens junctions."Oncogene. 19・35. 4022-4028 (2000)

[Publications] Yao,I.: "Association of membrane-associated guanylate kinase-interacting protein (MAGUIN)-1 with Raf-1."Biochem.Biophys.Res.Commun.. 270・2. 538-542 (2000)

[Publications] Fujiwara,T.: "Rho small G protein-dependent binding of mDia to a Src homology 3 domain-containing IRSp 53/BAIAP2 ."Biochem.Biophys.Res.Commun.. 271・3. 626-629 (2000)

[Publications] Takaishi,K.: "Mechanisms of activation and action of mDial in the formation of parallel stress fibers in MDCK cells."Biochem.Biophys.Res.Commun.. 274・1. 68-72 (2000)

[Publications] Yasuda,T.: "Importance of spatial activation of Cdc42 small G proteins by frabin for its functions in MDCK cells."Genes Cells. 5・7. 583-591 (2000)

[Publications] Takaishi,K.: "Multiple downstream signaling rathways from ROCK, a target molecule of Rho small G protein, in reorganization of the actin cytoskeleton in Madin-Darby canine kidney cells."Genes Cells. 5・11. 929-936 (2000)

[Publications] Peng,Y.F.: "Ankycorbin : A novel actin cytoskeleton-associated protein."Genes Cells. 5・12. 925-932 (2000)

[Publications] Mino,A.: "Membrane-associated guanylate kinase with inverted orientation(HAGI)-1/brain angiogenesis inhibitor 1-associated protein(BAP1) as a scaffolding molecule for Rap small G protein GDP/GTP exchange protein at tight junctions"Genes Cells. 5・12. 1009-1016 (2000)

[Publications] Suzuki,T.: "Rho family GTPase Cdc42 is essential for the actin-based motility of Shigella in mammalian cells."J.Exp.Med.. 191・11. 1905-1920 (2000)

[Publications] Mammoto A.: "Stimulation of Rho GDI relaease by ERM proteins."Methods Enzymol.. 325. 91-101 (2000)

[Publications] Matozaki,T.: "Small G protein networks : Their crosstalks and signal cascades."Cellular Signalling. 12・8. 515-524 (2000)

[Publications] Ozaki-Kuroda,K.: "Dynamic localization and function of Bnilp at the sites of directed growth in yeast Saccharomyces cerevisiae."Mol.Cell.Biol.. 21・3. 827-839 (2001)

[Publications] Takai,Y.: "Small GTP-binding proteins."Physiol.Rev.. 81・1. 153-208 (2001)

[Publications] Sakisaka,T.: "Requirement of interaction of Nectin-1α/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1."J.Virol.. (in press). (2001)

高井義美大阪大学, 医学系研究科, 教授 (60093514)