細胞の増殖・分化・死のシグナル伝達機構

• 研究課題/領域番号: 07CE2006
• 研究種目: COE形成基礎研究費
• 配分区分: 補助金
• 研究機関: 大阪大学
• 研究代表者: 祖父江 憲治 大阪大学, 医学系研究科, 教授 (20112047)
• 研究分担者: 長田 重一 大阪大学, 医学系研究科, 教授 (70114428) ; 中村 敏一 大阪大学, 医学系研究科, 教授 (00049397) ; 平野 俊夫 大阪大学, 医学系研究科, 教授 (40136718) ; 米田 悦啓 大阪大学, 医学系研究科, 教授 (80191667) ; 辻本 賀英 大阪大学, 医学系研究科, 教授 (70132735)
• 研究期間 (年度): 1995 – 1999
• 研究課題ステータス: 完了 (1999年度)
• 配分額: 1,070,000千円 (直接経費: 1,070,000千円); 1999年度: 380,000千円 (直接経費: 380,000千円); 1998年度: 360,000千円 (直接経費: 360,000千円); 1997年度: 330,000千円 (直接経費: 330,000千円)
• キーワード: カルデスモン / インターロイキン-6(IL-6) / 肝細胞増殖因子(HGF) / Fas因子 / bc1-2 / 核輸送 / 低分子暈型G蛋白質 / 細胞死 / 低分子量型G蛋白質

研究概要

祖父江は、平滑筋細胞形質がPI3キナーゼ/PKB(Akt)系とERKおよびp38MAPキナーゼ系の力のバランスにより決定されることを明らかにしたが、さらにこれらシグナル伝達系支配下にNkx-3.2,SRF,GATA6の3転写因子によるα1インテグリン遺伝子の平滑筋細胞特異的転写制御機構を解明した。また、mGluR1のシナプスへのターゲッティングに、シナプス後肥厚部に局在するPSD-Zip45が関与していることを証明した。
平野は、サイトカイン受容体gp130を介する細胞の増殖、生存シグナルにはSTAT3が重要な役割を果たしていることを昨年までに明らかにしたが、今年度はSTAT3の標的遺伝子として、c-myc,pim1/2を同定しこれらが協調して作用していることを示した。またpimの標的遺伝子としてVCPをみつけた。さらにgp130のシグナル特異的変異gp130発現マウスを作製し、STAT3とSHP2を介するシグナルが生体内で正と負に作用していることを証明した。
アポトーシスは染色体DNAの切断をともなっている。この過程にはカスパーゼによって活性化されるDNase(CAD)とその阻害たんぱく質(ICAD)が関与している。長田は、CAD,ICADの組換え蛋白質を合成し,CADは高い比活性を持つDNaseであること,ICADはCADの阻害因子としてばかりでなく、CADが合成される際,シャペロンとして作用することを示した。一方,カスパーゼ切断部位に変異を持つICADのトランスジェニクマウスの解析から、アポトーシスをおこした細胞をマクロファージが取り込み、そのDNAを分解しうることも示した。
米田は、Wnt/Winglessのシグナル伝達に重要な役割を果たす分子であるβ-cateninが、それ自身が持つ核膜孔複合体への結合能によって核へ移行し、その移行はRanに依存しない、新たな輸送経路であることを明らかにした。また、小胞体膜から核への情報伝達に関わる分子である SREBPが、アダプター分子を介することなく、importin-βに直接結合して輸送されることを証明した。さらに、importin-βのN末端側約半分の単独の結晶構造解析に初めて成功した。
倉智は、細胞生理に密接に連関するKチャネル(Kir)の局在について、Kir3.2は黒質ドーパミン神経樹状突起の後シナプス膜に局在すること、PDZ蛋白質がその局在に関与し得ること、さらにPDZ蛋白質はチャネルの活性制御も行うこと、脳下垂体で分泌小胞上のKir3.1/Kir3.4は分泌時に細胞膜へ移行し、機能すること、上皮細胞に発現するKir4.1は細胞により異なる極性に分布することを明らかにした。
辻本は、Bcl-2ファミリーたんぱくのミトコンドリアにおける機能ターゲットとして、外膜チャネルであるVDACを同定し、細胞死促進因子Bax/BakはVDACの開孔を通しシトクロムc遊離を誘導し、細胞死抑制因子Bcl-xLはVDACを閉孔することを示した。また、アポトーシスの実行過程の解析から、アポトーシスを特徴づける核クロマチン凝縮を誘導する新規因子Acinusを単離同定し、その機能解析を行った。
高井は、Rhoファミリー低分子量G蛋白質(Cdc42、Rac、Rho)の活性化機構と作用機構を明らかにすると共に、RhoファミリーとRabファミリー低分子量G蛋白質が協調的に作用して、細胞の運動と接着を制御することを見出した。また、Racによって制御されている新しい細胞間接着系NAP系が、カドヘリン.カテニン系の局在を制御し、上皮細胞の接着装置複合体の形成や維持に必須であることを明らかにした。
宮坂は、リンパ節へのリンパ球ホーミングを媒介する血管 HEVに特異的に発現する遺伝子の同定に成功した。また、リンパ球ホーミングを媒介する接着分子L-セレクチン、CD44の新規リガンドとして特殊なプロテオグリカン、バースカンを同定し、この分子間相互作用がL-セレクチン、CD44の糖鎖認識ドメインとバーシカン上のグリコサミノグリカン鎖を介するものであることを初めて明らかにした。
中村は、HGF gene therapyによりHGFが肝線維症/肝硬変の治療に有効であることを確認した。HGFが心筋の急性傷害に対する保護・修復因子であることを明らかにした。HGFは糖尿病ならびに糖尿病性腎症に対してもその発症・進行を抑制する効果をもつことを示した。また、HGFアンタゴニスト活性と血管新生阻害活性を合わせ持つHGF断片NK4はin vivoにおけるヒト膵癌の増殖・転移能を著名に抑制することを明らかにした。

研究成果

• [文献書誌] Nishida W. et al.: "Smooth muscle cell-specific transcription of α1 integrin gene mediated by Nkx3.2, SRF, and GATA6."EMBO.J.. (in press). (2000)
• [文献書誌] Tadokoro,S. et al.: "Involvement of unique leucine-Zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) ingroup 1 metabotropic glutamate receptor clustering."Proc.Natl.Acad.Sci.USA.. 96. 13801-13806 (1999)
• [文献書誌] Hayashi,K. et al.: "Changes in the balance of phosphoinositide 3-kinase/protein kinase B (Akt) and the mitogen-activated protein kinases (ERK/p38MAPK) determine the phenotype of visceral and vascular smooth muscle cells"J.Cell.Biol.. 145. 727-740 (1999)
• [文献書誌] Saga,H. et al.: "Phenotype-dependent expression of α-smooth muscle actin in visceral smooth muscle cells."Exp.Cell.Res.. 247. 279-292 (1999)
• [文献書誌] Yamada,Y. et al.: "Modulation of the channel activity of the e2/z1-subtype of N-Methyl D-Aspartate Receptor by PSD-95"J.Biol.Chem.. 247. 6647-6652 (1999)
• [文献書誌] Sobue,K. et al.: "Expressional regulation of smooth muscle cell-specific genes in association with phenotypic modulation."Mol.Cell.Biochem.. 190. 105-118 (1999)
• [文献書誌] Itoh,M. et al.: "A role of Gab1 for heart, placenta, and skin development, and growth factors- and cytokine-induced ERK MAP kinase activation."Mol.Cell.Biol.. (in press). (2000)
• [文献書誌] Tanaka,H. et al.: "GATA-1 blocks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and Bcl-2 in a murine myeloid cell line M1."Blood. 95. 1264-1273 (2000)
• [文献書誌] Ohtani,T. et al.: "Dissection of signaling cascades through gp130 in vivo : Reciprocal roles for STAT3- and SHP2-mediated signals in immune responses."Immunity. 12. 95-105 (2000)
• [文献書誌] Shirogane,T. et al.: "Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and anti-apoptosis."Immunity. 11. 709-719 (1999)
• [文献書誌] Fekany,K. et al.: "The zebrafish bozozok locus encodes Dharma, a homeodomain protein essential for induction of gastrula organizer and dorsoanterior embryonic structures."Development. 126. 1427-1438 (1999)
• [文献書誌] Kiuchi,N. et al.: "STAT3 is required for the gp130-mediated full activation of the c-myc gene."J.Exp.Med.. 189. 63-73 (1999)
• [文献書誌] Ueki,T. et al.: "Hepatocyte growth factor gene therapy of liver cirrhosis in rats."Nat.Medicine.. 5. 226-230 (1999)
• [文献書誌] Tahara,M. et al.: "Hepatocyte gowth factor leads to recovery from alcohol-induced fatty liver in rats."J.Clin.Invest.. 103. 313-320 (1999)
• [文献書誌] Sun,W. et al.: "Differential expression of hepatocyte growth factor and its receptor, c-Met in the rat retina during development."Brain Res.. 851. 46-53 (1999)
• [文献書誌] Matsumoto,K. et al.: "Prevention of renal damage by Angiotensin II blockade, accompanied by increased renal hepatocyte growth factor in experimental hypertensive rats."Hypertension.. 34. 279-284 (1999)
• [文献書誌] Sumi,T. et al.: "Cofilin phosphorylation and actin cytoskeletal dynamics regulated by Rho-and Cdc42-activated LIM-kinase2."J.Cell.Biol.. 147. 1519-1532 (1999)
• [文献書誌] Kawano,Y. et al.: "Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo."J.Cell.Biol.. 147. 1023-1037 (1999)
• [文献書誌] Tamada,K. et al.: "Ni,J.,and Chen,L.: Modulation of T cell-mediated immunity in tumor and graft versus host disease models through LIGHT costimulatory pathway."Nat.Med.. (in press). (2000)
• [文献書誌] McIloy,D. et al.: "An auxiliary mode of apoptotic DNA fragmentation provided by phagocytes."Genes & Develop.. (in press). (2000)
• [文献書誌] Yokoyama,H. et al.: "A novel activation mechanism of caspase-activated DNase from Drosophila melanogaster."J.Biol.Chem.. (in press). (2000)
• [文献書誌] Sakahira,H. et al.: "Specific chaperone-like activity of inhibitor of caspase-activated DNase for caspase-activated DNase."J.Biol.Chem.. (in press). (2000)
• [文献書誌] McIloy,D. et al.: "Involvement of caspase 3-activated DNase in internucleosomal DNA cleavage induced by diverse apoptotic stimuli."Oncogene. 18. 4401-4408 (1999)
• [文献書誌] Nagata,S.: "Fas ligand-induced apoptosis."Annu.Rev.Genetics.. 33. 29-55 (1999)
• [文献書誌] Shimizu,S. et al.: "Electrophysiological study of a novel large pore formed by Bax and VDAC, which is permeable to cytochrome c."J.Biol.Chem.. (in press). (2000)
• [文献書誌] Shimizu,S. et al.: "BH4 domain of anti-apoptotic Bcl-2 family members closes VDAC, and inhibits apoptotic mitochondrial changes and cell death."Proc.Natl.Acad.Sci.USA.. (in press). (2000)
• [文献書誌] Shimizu,Y. et al.: "Pro-apoptotic BH3-only Bcl-2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate VDAC activity."Proc.Natl.Acad.Sci.USA.. 97. 577-582 (2000)
• [文献書誌] Sahara,S. et al.: "Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation."Nature. 401. 168-173 (1999)
• [文献書誌] Shimizu,S. et al.: "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC."Nature. 399. 483-487 (1999)
• [文献書誌] Imazu,T. et al.: "Bcl-2/E1B 19 kDa-interacting protein 3-ike protein (Bnip3L) interacts with Bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permeability."Oncogene. 18. 4523-4529 (1999)
• [文献書誌] Kitamura,H. et al.: "Tertiapin potently and selectively blocks muscarinic K+ channels in rabbit cardiac myocytes."J.Pharm.Exp.Therapeutics. (in press). (2000)
• [文献書誌] Shindo,T. et al.: "MCC-134, a novel vascular refaxing agent, is an inverse agonist for the pancreactic type of ATP-sensitive K+ channel."J.Pharm.Exp.Therapeutics. 292. 131-135 (2000)
• [文献書誌] Hibino,H. et al.: "Anchoring proteins confer G protein sensitivity to an inwardly rectifying K+ channel through the GK domain."EMBO.J.. 19. 78-83 (2000)
• [文献書誌] Repunte,VP. et al.: "Extracellular links in Kir subunits control the unitary conductacne of SUR/Kir6.0 ion channels."EMBO.J.. 18. 3317-3324 (1999)
• [文献書誌] Morishige,K. et al.: "Secretagogue-induced exocytosis recruits G protein-gated K+ channels to plasma membrane in endocrine cells."J.Biol.Chem.. 274. 7969-7974 (1999)
• [文献書誌] Inanobe,A. et al.: "Characterization of G protein-gated K+ channels composed of Kir3.2 subunits in substantia nigra."J.Neurosci.. 19. 1006-1017 (1999)
• [文献書誌] Iizuka,T. et al.: "Stage-specific expression of mucosal addressin cell adhesion molecule-1 during embryogenesis in rats."J.Immunol.. (in press). (2000)
• [文献書誌] Ishiwatari,H. et al.: "Requirements for signal delivery through CD44: Analysis using CD44-Fas chimeric proteins."J.Immunol.. 163. 1258-1264 (1999)
• [文献書誌] Izawa,D. et al.: "Expression profile of active genes in mouse lymph node high endothelial cells"Int.Immunol.. 11. 1989-1997 (1999)
• [文献書誌] Pabst,R. et al.: "More than an interaction of lymphocytes with endothelial cells of the high endothelial venules via adhesion molecules."The Immunologist.. 7. 1-2 (1999)
• [文献書誌] Kawashima,H. et al.: "Identification and characterization of ligands for L-selectin in the kidney. I, Versican, a large chondroitin sulfate proteoglycan, is a ligand for L-selectin."Int.Immunol.. 11. 393-405 (1999)
• [文献書誌] Hiraoka,N. et al.: "A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewisx, an L-selectin ligand displayed by CD34."Immunity.. 11. 79-89 (1999)
• [文献書誌] Haraguchi,T. et al.: "Live fluorescence imaging reveals early recruitment of emerin, LBR, HP1β and RanBP2 to reforming functional nuclear envelope."J.Cell.Sci.. (in press). (2000)
• [文献書誌] Hieda,M. et al.: "A monoclonal antibody to the C-terminal acidic portion of Ran inhibits both the recycling of Ran and nuclear protein improt in living cells."J.Cell.Biol.. 144. 645-655 (1999)
• [文献書誌] Yokoya,F. et al.: "β-Catenin can be transported into the nucleus in Ran-unassisted manner."Mol.Biol.Cell.. 10. 1119-1131 (1999)
• [文献書誌] Nagoshi,E. et al.: "Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor occurs through the direct interaction of importin β with HLH-Zip."Mol.Biol.Cell.. 10. 2221-2233 (1999)
• [文献書誌] Takagi,M. et al.: "Chmadrin : a novel Ki-67 antigen-related perichromosomal protein possibly implicated in higher order chromatin structure."J.Cell.Sci.. 112. 2463-2472 (1999)
• [文献書誌] Kose,S. et al.: "β-Subunit of nuclear pore-targeting complex (importin-β) can be exported from the nucleus in a Ran-independent mannor."J.Biol.Chem.. 274. 3946-3952 (1999)
• [文献書誌] Satoh-Horikawa,K. et al.: "Nectin-3: A new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities."J.Biol.Chem.. (in press). (2000)
• [文献書誌] Kawabe,H. et al.: "nArgBP2, a novel neural member of Ponsin/ArgBR2/Vinexin family that interacts with Synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP)."J.Biol.Chem.. 274. 30914-30918 (1999)
• [文献書誌] Mammoto,A. et al.: "Rab11BP/Rabphilin-11: A downstream targer of rab11 small G protein implicated in vesicle recycling."J.Biol.Chem.. 274. 25517-25524 (1999)
• [文献書誌] Umikawa,M. et al.: "Association of frabin with the actin cytoskeleton is essential for microspike formation through activation of Cdc42 small G protein."J.Biol.Chem.. 274. 25197-25200 (1999)
• [文献書誌] Ikeda,W. et al.: "Afadin : A key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis."J.Cell.Biol.. 146. 1117-1132 (1999)
• [文献書誌] Fujiwara,T. et al.: "Bnilp regulates microtubule-dependent nuclear migration through the actin cytoskeleton in Saccharomyces cerevisiae."Mol.Cell.Biol.. 19. 8016-8027 (1999)
• [文献書誌] Kashiwada K.et al.: "Coordinate expression of a-tropomyosin and caldesmon isoforms in association with phenotypic mudulation of smooth muscle cells." J.Biol.Chem.272. 15396-15404 (1997)
• [文献書誌] Saga H.et al.: "Paradoxical expression of α-smooth muscle actin in visceral and vascular smooth muscle cells in their phenotype-dependent manner." Exp.Cell Res.in press. (1998)
• [文献書誌] Obata H.et al.: "Smooth muscle cell phenotype-dependent transcriptional regulation of the α1 integrin gene." J.Biol.Chem.272. 26643-26651 (1997)
• [文献書誌] Sobue K et al.: "Phenotype-dependent gene regulation of smooth muscle,cell-specific cytoskeletal proteins." Mol.Cell.Biol.(in press). (1998)
• [文献書誌] Hayashi K.et al.: "IGF-I generating signalling mediated by phosphatidylinositol 3-kinase and Akt(protein kinase B)is essential for maintainig a differentiated phenotype of smooth muscle cells." EMBO J.(in press). (1998)
• [文献書誌] Nishida W.et al.: "Recruitment of Bagpippe homologue(homeobox protein)in SRF-dependent transcription of smooth muscle cell-specific genes." Proc.Natl.Acad.Sci.USA. (in press). (1998)
• [文献書誌] Fujitani Y.et al.: "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT." Oncogene. 14. 751-761 (1997)
• [文献書誌] Takahashi-Tezuka,M.et al.: "Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK." Oncogene. 14. 2273-2282 (1997)
• [文献書誌] Ihara S.et al.: "Dual control of neurite outgrowth by STAT3 and MAP kinase in PC12 cells stimulated with interleukin-6." EMBO J.16. 5345-5352 (1997)
• [文献書誌] Shimozaki K.et al.: "Involvement of STAT3 in the granulocyte colony stimulating factor-induced differentiation of myeloid cells." J.Biol.Chem.(in press). (1998)
• [文献書誌] Amato S.et al.: "Transcriptional regulation of the junB gene in B lymphocytes : role of protein kinase A and a membrane immunoglobulin-regulated protein phosphatase." J.Immunol.159. 4676-4685 (1997)
• [文献書誌] Hirano T.: "Interleukin 6 and its receptor : Ten years later." Int.Reviews of Immunology. (in press). (1998)
• [文献書誌] Nagata,S.: "Apoptosis by death factor." Cell. 88. 355-365 (1997)
• [文献書誌] Kondo T.et al.: "Essential roles of the Fas ligand in the development of hepatitis." Nature Med.3. 409-413 (1997)
• [文献書誌] Tanaka M.et al.: "Lethal effect of recombinant human Fas ligand in mice pretreated with Propionibacterium Acnes." J.Immunol.158. 2303-2309 (1997)
• [文献書誌] Ishiwatari-Hayasaka,H.et al.: "Induction of cell death by chimeric L-selectin-Fas receptors." Int.Immunol.9. 627-635 (1997)
• [文献書誌] Shimoda K.et al.: "Jakl plays an essential role for receptor phosphorylation and Stat activation in response to granulocyte colony-stimulating factor." Blood. 90. 597-602 (1997)
• [文献書誌] Itoh N.et al.: "Requirement of Fas for the development of autoimmune diabetes in non-obese diabetic mice." J.Exp.Med.186. 613-618 (1997)
• [文献書誌] Orita T.et al.: "Binding of NF-Y transcription factor to one of cis-elements in the myeloperoxidase gene promoter that responds to G-CSF." J.Biol.Chem.272. 23216-23223 (1997)
• [文献書誌] Tsutsui T.et al.: "Administration of IL-12 induces a CD3+CD4-CD8-B220+lymphoid population capable of eliciting cytolysis against Fas-positive tumor cells." J.Immunol.159. 2599-2605 (1997)
• [文献書誌] Xu,X.-N.et al.: "Evasion of CTL responses by nef-dependent induction of Fas ligand(CD95L)expression on SIV-infected cells." J.Exp.Med.186. 7-16 (1997)
• [文献書誌] Bahr,G.M.et al.: "Elevated serum level of Fas-ligand(FasL)correlates with the asymptomatic stage of HIV-infection." Blood. 90. 896-898 (1997)
• [文献書誌] Watanabe M.et al.: "Gene transfection of mouse primordial germ cells in vitro and analysis of their survival and growth control." Exp.Cell Res.230. 76-83 (1997)
• [文献書誌] Takahashi T..et al.: "Overexpression of Bcl-xL prevents bacterial superantigen-induced apoptosis of thymocytes in vitro." Cell Death & Differ.4. 159-165 (1997)
• [文献書誌] Yasuhara N.et al.: "Essential role of active nuclear transport in apoptosis." Genes to Cells. 2. 55-64 (1997)
• [文献書誌] Shigenaga A.et al.: "Targeted expression of ced-3 and Ice induces programmed cell death in Drosophila." Cell Death & Differ.(in press). (1998)
• [文献書誌] Eguchi Y.et al.: "Intracellular ATP levels determine cell death fate by apoptosis or necrosis." Cancer Res.57. 1835-1840 (1997)
• [文献書誌] Kamada S.et al.: "Caspase-4 and caspase-5,members of the ICE/CED-3 family of cystein proteases,are CrmA-inhibitable proteases." Cell Death & Differ.(in press). (1998)
• [文献書誌] Kamada S.et al.: "Involvement of caspase-4(-like)protease in Fasmediated apoptotic pathway." Oncogene. 15. 285-290 (1997)
• [文献書誌] Ohtsu M.et al.: "Inhibition of apoptosis by the actin-regulatory protein gelsolin." EMBO J.16. 4650-4656 (1997)
• [文献書誌] Yasuhara N.et al.: "Evidence against a functional site for Bcl-2 downstream of caspase cascade in preventing apoptosis." Oncogene. 15. 1921-1928 (1997)
• [文献書誌] Kitanaka C.et al.: "Caspase-dependent apoptosis of COS-7 cells induced by Bax overexpression : differential effects of Bcl-2 and Bcl-xL on Bax-induced caspase activation and apoptosis." Oncogene. 15. 1763-1772 (1997)
• [文献書誌] Wada M.et al.: "Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins." J.Biol.Chem.272. 3875-3878 (1997)
• [文献書誌] Fukui K.et al.: "Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins." J.Biol.Chem.272. 4655-4658 (1997)
• [文献書誌] Horio Y.et al.: "Clustering and enhanced activity of an inwardly rectifying potassium channel,kir4.1,by an anchoring protein,PSD-95/SAP90." J.Biol.Chem.272. 12885-12888 (1997)
• [文献書誌] Orita S.et al.: "Physical and functional interactions of Doc2 and Munc13 in Ca2+-dependent exocytotic machinery." J.Biol.Chem.272. 16081-16084 (1997)
• [文献書誌] Imamura H.et al.: "Bni1p and Bnr1p : Downstream targets of the Rho family small G proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae." EMBO J.16. 2745-2755 (1997)
• [文献書誌] Kotani H.et al.: "Rho regulates association of both the ERM family and vinculin with the plasma membrane in MDCK cells." Oncogene. 14. 1705-1713 (1997)
• [文献書誌] Takahashi K.et al.: "Direct interaction of Rho GDI with Ezrin/Radixin/Moesin initiates the activation of Rho small G protein." J.Biol.Chem.272. 23371-23375 (1997)
• [文献書誌] Koch G.et al.: "Association of the Rho family small GTP-binding proteins with Rho GDP dissociation inhibitor(Rho GDI)in Saccharomyces cerevisiae." Oncogene. 15. 417-422 (1997)
• [文献書誌] Eguchi H.et al.: "A nuclear localization signal of human aryl hydrocarbon receptor nuclear translocator/hypoxia-inducible factor 1 β is a novel bipartite type recognized by the two components of nuclear poretargeting complex." J.Biol.Chem.272. 17640-17647 (1997)
• [文献書誌] Kose S.et al.: "Ran-unassisted nuclear migration of a 97kDa component of nuclear pore-targeting complex,occurring in a facilitated manner." J.Cell Biol.139. 841-849 (1997)
• [文献書誌] Miyamoto Y.et al.: "Defferential modes of nuclear localization signal(NLS)recognition by three distinct classes of NLS-receptors." J.Biol.Chem.272. 26375-26381 (1997)
• [文献書誌] Takai K.et al.: "Hepatocyte growth factor is constitutively produced by human bone marrow stromal cells and promotes erythropoiesis." Blood. 89. 1560-1565 (1997)
• [文献書誌] Weimar,I.S.et al.: "Hepatocyte growth factor/scatter factor(HGF/SF)promotes adhesion of lymphoma cells to extra-cellular matrix molecules via α4β,and α5β,integrens." Blood. 89. 990-1000 (1997)
• [文献書誌] Liu,K.et al.: "Change in hepatic handling of hepatocyte growth factor during liver regeneration in rats." Am.J.Physiol.(in press). (1998)
• [文献書誌] Torok N.et al.: "Upregulation of molecular motor encoding genes during HGF-and EGF-induced cell motility." J.Biol.Chem.(in press). (1998)
• [文献書誌] Nakamura T.et al.: "Induction of hepetocyte growth factor in fibroblasts by tumor-derived factors effects invasive growth of tumor cells : In vitro analysis of tumor-stromal interaction." Cancer Res.57. 3305-3313 (1997)
• [文献書誌] Ishiwatari-Hayasaka,H.et al.: "Induction of cell death by chimeric L-selectin-Fas receptors." Int.Immunol.9. 627-635 (1997)
• [文献書誌] Koyanagi Y.et al.: "Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain." J.Virol.71. 2417-2424 (1997)
• [文献書誌] Yamada M.et al.: "Sulfonylurea receptor 2B and Kir6.1 form a sulfonilurea-sensitive but ATP-insensitive K+channel." J.Physiol.499. 715-720 (1997)
• [文献書誌] O Horio Y.et al.: "Clustering and enhanced activity of an inwardly rectifying potassium channel,Kir4.1,by an anchoring protein,PSD-95/SAP90 family." J.Biol.Chem.272. 12885-12888 (1997)
• [文献書誌] Hibino H.et al.: "An ATP-dependent inwardly rectifying potassium channel,KAB-2(Kir4.1),in cochlear stria vascularis of inner ear : its specific subcellular localization and correlation with the formation of endocochlear potential." J.Neurosci.17. 4711-4721 (1997)
• [文献書誌] Ishii M.et al.: "Expression and clustered distribution of an inwardly rectifying potassium channel,KAB-2/Kir4.1,on mammalian retinal muller cell membrane ; Their regulation by insulin and laminin signals." J.Neurosci.17. 7725-7735 (1997)