Researcher Database

SABE Hisataka
Faculty of Medicine Physiological Science Biochemistry
Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Medicine Physiological Science Biochemistry

Job Title

    Professor

Degree

  • (BLANK)
  • (BLANK)

URL

Research Interests

  • Arf6   paxillin   endocytosis   p130Cas   AMAP1   E-cadherin   PAG3   endosomal recycling   ARF   AMAP2   GEP100   Git1   PAGs   ArfGAP   Molecular Cell Biology   

Research Areas

  • Basic medicine / General medical chemistry

Academic & Professional Experience

  • 1986    Instructor, Kyoto University School of Medicine
  • 1990    The Rockefeller University Laboratory of
  • Molecular Oncology Postdoctoral Associate
  • 1993    The Rockefeller University Laboratory of
  • Molecular Oncology Assistant Professor
  • 1994    Associate Professor, Institute for Virus Research, Kyoto University
  • 1998    Head, Department of Molecular Biology, Osaka Bioscience Institute
  • 1999    Visiting Professor, Kyoto University
  • 2000    Visiting Professor, Osaka Uinversity

Education

  •        - 1986  Kyoto University  Graduate School, Division of Medicine  japan
  •        - 1980  Kyoto University  Faculty of Science  japan

Association Memberships

  • JAPAN SOCIETY FOR CELL BIOLOGY   

Research Activities

Published Papers

Books etc

  • Properties of human IL2 receptor expressed on non-lymphoid cells by cDNA transfection.(共著)
    ()
    Mol.Biol.Med. 1984
  • Interleukin 2 receptor ; structure, function, and expression.(共著)
    ()
    Cold Spring Harbor Symposia on Quantitative Biology 1986
  • Activation of c-Src in cells bearing v-Crk and its suppression by Csk.(共著)
    ()
    Mol.Cell.Biol. 1992
  • Analysis of Csk SH2 binding to tyrosine phosphorylated proteins in c-Src suppression and mitotic activation.(共著)
    ()
    Proc.Natl.Acad.Sci.USA 1994
  • Growth factors and receptors of lymphocytes.(共著)
    ()
    Acta Neurochiurgica (eds.K.Sano and S.Ishii, Springer-Verlag, NY, USA) 1987
  • Interleukin 2 receptor.(共著)
    ()
    The molecular Biology of Receptor (eds.A.D.Strosberg, Ellis Horwood Ltd., Chichester, England) 1988

Conference Activities & Talks

MISC

  • 真崎雄一, 小野寺康仁, 東恒仁, 堀之内孝広, 及川司, 佐邊壽孝  日本細胞生物学会大会(Web)  69th-  ROMBUNNO.T8‐11(P1‐077) (WEB ONLY)  2017   [Not refereed] [Not invited]
  • 古川聖太郎, 橋本あり, 橋本茂, 小野寺康仁, 及川司, 大塚勇太郎, 佐邊壽孝, 平野聡  日本外科学会定期学術集会(Web)  116th-  PS-002-2 (WEB ONLY)  -002  2016/04   [Not refereed] [Not invited]
  • Y. Komiya, Y. Onodera, M. Kuroiwa, S. Nomimura, Y. Kubo, J. M. Nam, J. M. Nam, K. Kajiwara, S. Nada, C. Oneyama, H. Sabe, M. Okada  Oncogenesis  5-  2016/09   [Not refereed] [Not invited]  
    © 2016 The Author(s). Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial-mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth. In the present study, ARHGEF5 was upregulated during tumor growth factor-β-induced EMT in human epithelial MCF10A cells, and promoted cell migration by activating the Rho-ROCK pathway. ARHGEF5 was necessary for the invasive and in vivo metastatic activity of human colorectal cancer HCT116 cells. These findings underscore the crucial role of ARHGEF5 in cell migration and invasion/metastasis. An in vivo tumorigenesis assay revealed that ARHGEF5 had the potential to promote tumor growth via the phosphatidylinositol 3-kinase (PI3K) pathway. However, ARHGEF5 was not required for tumor growth in epithelial-like human colorectal cancer HCT116 and HT29 cells, whereas the growth of mesenchymal-like SW480 and SW620 cells depended on ARHGEF5. Induction of EMT by tumor necrosis factor-α or Slug in HCT116 cells resulted in the dependence of tumor growth on ARHGEF5. In these mesenchymal-like cells, Akt was activated via ARHGEF5 and its activity was required for tumor growth. Analysis of a transcriptome data set revealed that the combination of ARHGEF5 upregulation and E-cadherin downregulation or Snail upregulation was significantly correlated with poor prognosis in patients with colorectal cancers. Taken together, our findings suggest that EMT-induced ARHGEF5 activation contributes to the progression of tumor malignancy. ARHGEF5 may serve as a potential therapeutic target in a subset of malignant tumors that have undergone EMT.
  • 小野寺康仁, 堀川芽衣, 佐邊壽孝  がんと代謝研究会プログラム&抄録集  4th-  44  2016/07   [Not refereed] [Not invited]
  • p53はEZH2と機能的に競合することで上皮性維持に寄与する
    及川 司, 大塚 勇太郎, 小野寺 康仁, 半田 悠, 橋本 あり, 橋本 茂, 鈴木 穣, 佐邊 壽孝  日本癌学会総会記事  75回-  J  -3030  2016/10   [Not refereed] [Not invited]
  • メバロン酸経路阻害剤スタチンはArf6経路を高発現する癌に有効である
    橋本 あり, 橋本 茂, 及川 司, 大塚 勇太郎, 半田 悠, 小野寺 康仁, 佐邊 壽孝  日本生化学会大会プログラム・講演要旨集  89回-  [1P  -268]  2016/09   [Not refereed] [Not invited]
  • 代謝と細胞動態 細胞動態・運命決定を司る内なるチカラ 代謝と輸送および区画化を介したがん形質の誘導
    小野寺 康仁, Bissell Mina, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  68回-  21  -21  2016/05   [Not refereed] [Not invited]
  • 小野寺康仁, BISSELL Mina, 佐邊壽孝  日本細胞生物学会大会(Web)  68th-  ROMBUNNO.S11‐2 (WEB ONLY)  2016   [Not refereed] [Not invited]
  • 橋本あり, 橋本茂, 及川司, 大塚勇太郎, 半田悠, 小野寺康仁, 佐邊壽孝  日本生化学会大会(Web)  89th-  ROMBUNNO.1P‐268 (WEB ONLY)  2016   [Not refereed] [Not invited]
  • 小野寺康仁, 南ジンミン, 白土博樹, 佐邊壽孝  日本放射線影響学会大会抄録(Web)  59th-  ROMBUNNO.W12‐1 (WEB ONLY)  2016   [Not refereed] [Not invited]
  • p53はエピジェネティック制御を介して上皮性を維持する
    及川 司, 小野寺 康仁, 大塚 勇太郎, 半田 悠, 橋本 あり, 橋本 茂, 鈴木 穣, 佐邊 壽孝  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  88回・38回-  [2P1108]  -[2P1108]  2015/12   [Not refereed] [Not invited]
  • Arf6-AMAP1経路によるROS制御は乳癌の放射線抵抗性に寄与する
    小野寺 康仁, 南 ジンミン, 及川 司, 白土 博樹, 佐邊 壽孝  日本癌学会総会記事  74回-  E  -1049  2015/10   [Not refereed] [Not invited]
  • 放射線照射後の乳腺上皮細胞の3次元構造維持に関わる分子機序の解析
    南 ジンミン, 小野寺 康仁, 佐邊 壽孝, 白土 博樹  日本癌学会総会記事  74回-  P  -2343  2015/10   [Not refereed] [Not invited]
  • Grb2はEGF刺激によるGEP100-Arf6経路活性化を介した腫瘍浸潤転移能を促進する
    毛受 暁史, 今村 直人, 祢里 真也, 長 博之, 中西 崇雄, 志熊 啓, 曽和 晃正, 園部 誠, 佐邊 壽孝, 伊達 洋至  日本癌学会総会記事  74回-  P  -2121  2015/10   [Not refereed] [Not invited]
  • 小野寺康仁, 南ジンミン, 白土博樹, BISSELL Mina, 佐邊壽孝  がんと代謝研究会プログラム&抄録集  3rd-  44  2015   [Not refereed] [Not invited]
  • 腎盂尿管癌におけるEPB4.1L5発現の意義
    大門 達明, 小坂 威雄, 菊地 栄次, 三上 修治, 宮崎 保匡, 橋本 あり, 橋本 茂, 水野 隆一, 宮嶋 哲, 岡田 保典, 佐邊 壽孝, 大家 基嗣  日本癌学会総会記事  74回-  P  -3251  2015/10   [Not refereed] [Not invited]
  • Arf6-AMAP1経路によるROS制御は乳癌の放射線抵抗性に寄与する
    小野寺 康仁, 南 ジンミン, 及川 司, 白土 博樹, 佐邊 壽孝  日本癌学会総会記事  74回-  E  -1049  2015/10   [Not refereed] [Not invited]
  • 放射線照射後の乳腺上皮細胞の3次元構造維持に関わる分子機序の解析
    南 ジンミン, 小野寺 康仁, 佐邊 壽孝, 白土 博樹  日本癌学会総会記事  74回-  P  -2343  2015/10   [Not refereed] [Not invited]
  • Grb2はEGF刺激によるGEP100-Arf6経路活性化を介した腫瘍浸潤転移能を促進する
    毛受 暁史, 今村 直人, 祢里 真也, 長 博之, 中西 崇雄, 志熊 啓, 曽和 晃正, 園部 誠, 佐邊 壽孝, 伊達 洋至  日本癌学会総会記事  74回-  P  -2121  2015/10   [Not refereed] [Not invited]
  • 新規NFκB抑制メカニズムとしてのAMAP1
    芦田 昇, Nguyen Tien Dat, 岸畑 雅子, 吉川 歩, 佐邊 壽孝, 亀井 加恵子, 荒井 秀典, 北 徹, 横出 正之, 木村 剛  日本臨床分子医学会学術総会プログラム・抄録集  51回-  100  -100  2014/04   [Not refereed] [Not invited]
  • 腎盂尿管癌におけるEPB4.1L5発現の意義
    大門 達明, 小坂 威雄, 菊地 栄次, 三上 修治, 宮崎 保匡, 橋本 あり, 橋本 茂, 水野 隆一, 宮嶋 哲, 岡田 保典, 佐邊 壽孝, 大家 基嗣  日本癌学会総会記事  74回-  P  -3251  2015/10   [Not refereed] [Not invited]
  • Arf6-AMAP1経路による酸化還元状態の恒常性維持は乳癌の放射線抵抗性に寄与する(Robust redox homeostasis mediated by Arf6-AMAP1 pathway confers resistance to ionizing radiation in breast cancer)
    小野寺 康仁, 南 ジンミン, 及川 司, 白土 博樹, 佐邊 壽孝  日本癌学会総会記事  73回-  E  -3010  2014/09   [Not refereed] [Not invited]
  • EZH2発現亢進により創出されるArf6を中心とした間葉浸潤に特化した分子装置は腎癌の予後不良に関与する(EZH2 generates Arf6-based mesenchymal invasion machinery that is central to poor prognosis of renal cancer)
    橋本 茂, 杉野 弘和, 橋本 あり, 吉河 歩, 及川 司, 半田 悠, 大家 基嗣, 三上 修治, 佐邊 壽孝  日本癌学会総会記事  73回-  J  -2075  2014/09   [Not refereed] [Not invited]
  • 乳癌において変異p53がリガンド反応性の間葉型浸潤分子装置を創出する機序(TP53 alterations generate Arf6-based mesenchymal invasion pathway that is activated by RTKs and TGFβ1 in breast cancer)
    橋本 あり, 橋本 茂, 杉野 弘和, 吉河 歩, 及川 司, 小野寺 康仁, 半田 悠, 大塚 勇太郎, 岩見 昴亮, 小根山 千歳, 岡田 雅人, 福田 光則, 佐邊 壽孝  日本癌学会総会記事  73回-  J  -2077  2014/09   [Not refereed] [Not invited]
  • p53は間葉系形質を持つ乳がん細胞に上皮系形質を再獲得させる(p53 recalls epithelial memory in mammary cancer cells with mesenchymal phenotypes)
    及川 司, 小野寺 康仁, 橋本 あり, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  73回-  P  -1159  2014/09   [Not refereed] [Not invited]
  • Shigeru Hashimoto, Ari Hashimoto, Hirokazu Sugino, Ayumu Yoshikawa, Haruka Handa, Masanao Yoshino, Yutaro Otsuka, Hisataka Sabe  Ras Superfamily Small G Proteins: Biology and Mechanisms 2: Transport  253  -274  2014/05   [Not refereed] [Not invited]  
    © 2014 Springer International Publishing Switzerland. All rights reserved.While Arf-family small GTPases (Arf-GTPases) consist of 5 members in humans, 31 human genes have been identified that encode proteins bearing the GTPase-activating protein (GAP) domain for Arf-GTPases. Interestingly, Arf1, the first identified Arf, was shown to substantially lack intrinsic GTPase activity, which other Ras-superfamily members of small GTPases generally bear. Likewise, ArfGAP domains primarily consist of zinc-finger structures, and do not resemble GAP domains for other small GTPases. Arfs primarily function in intracellular vesicle/membrane trafficking. A general model shows that Arfs play roles in membrane budding, in which GTP-Arfs recruit coatomer proteins to generate and maintain membrane curvature to initiate the budding. Coatomers are thought to be separated from Arf-mediated vesicles before they reach the target membrane, while this separation may or may not be coupled with the GTP hydrolysis activity. We have shown that several ArfGAPs, such as AMAP1 and AMAP2, have the ability to bind stably to GTP-Arf6, without immediate GTP hydrolysis. They each contain a BAR domain and hence may act as coatomers for Arf-mediated vesicles. These ArfGAPs moreover act to recruit their binding proteins to sites of Arf6 activation, which are not coatomer components. These findings have amended the classical, general model of the functions of ArfGAPs, as well as Arf-GTPases. In this review, we will describe the recent information revealed about ArfGAPs, with the aim to decipher and discuss their fundamental roles.
  • 乳癌における放射線照射後の浸潤能獲得過程に関わる分子機序の解析(Analysis of molecular mechanism involved in invasiveness of radiation treated breast cancer cells)
    南 ジンミン, 小野寺 康仁, 佐邊 壽孝, 白土 博樹  日本癌学会総会記事  73回-  P  -1450  2014/09   [Not refereed] [Not invited]
  • K. Miura, Y. Wakayama, M. Tanino, Y. Orba, H. Sawa, M. Hatakeyama, S. Tanaka, H. Sabe, N. Mochizuki  Oncogene  32-  5292  -5301  2013/11   [Not refereed] [Not invited]  
    Shp2 is a positive regulator for Erk activation downstream of receptor tyrosine kinases for growth factors. It has been controversial how Shp2 induces Erk activation. We here demonstrate that EphA2 is responsible for Shp2-mediated Erk activation by phosphorylating Tyr542 and Tyr580 of Shp2 in the cells stimulated with growth factors. In NMuMG mammary epithelial cells stimulated with hepatocyte growth factor (HGF), HGF-dependent Erk phosphorylation was prolonged only in the presence of EphA2. This Erk activation paralleled the phosphorylation of Tyr542/580 of Shp2 and the association of Grb2 with Shp2, suggesting the positive signal involving Grb2 signal to activate Ras-Erk pathway. Immunohistochemical studies of mammary cancer specimens revealed that the cancer progression was associated with both Tyr580 phosphorylation of Shp2 and increased expression of EphA2, which were also correlated with increased Erk phosphorylation. Overexpression of either Shp2Thr468Met (a phosphatase- defective mutant found in Lentigines, Electrocardiographic abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth and sensorineural Deafness (LEOPARD) syndrome) or Shp2Asn308Asp (a phosphatase-active mutant found in Noonan syndrome) with EphA2 exhibited comparable activation of Erk and stronger activation than wild-type Shp2, suggesting the phosphatase-independent Erk activation. Expression of Shp2Thr468Met with Tyr542/580Phe mutations resulted in the suppression of Erk activation. Phosphatase-active and -inactive, and wild-type Shp2s bound equally to Grb2, suggesting that phosphorylation of Tyr542/580 of Shp2 was essential but not sufficient for Shp2-mediated Erk activation. We found that Gab1 (Grb2-associated binder 1) was involved in the mutant Shp2-mediated Erk activation. Zebrafish injected with Shp2Thr468Met mRNA showed cardiac edema, whereas those depleted of EphA2b showed less phenotype, suggesting that EphA2 might partly account for the phenotype of LEOPARD syndrome. Collectively, tyrosine phosphorylation of Shp2 by EphA2 contributes to the phosphatase-independent Shp2-mediated activation of Erk and might be involved in Shp2-associated diseases. © 2013 Macmillan Publishers Limited.
  • 癌放射線治療への分子生物学的アプローチ 変異p53が放射線抵抗性に根幹的な間葉型浸潤経路を創出する機構(Toward the improvement of radiotherapy: Approaches from the molecular biological point of view Mechanisms by which oncogenic mutant-p53 generates mesenchymal invasive pathway pivotal to a radiation resis
    佐邊 壽孝, 橋本 あり, 橋本 茂, 小野寺 康仁, 及川 司, Nam Jin-Min, 小根山 千歳, 杉野 弘和, 吉河 歩, 大塚 勇太郎, 半田 悠, 芳野 正修, 岡田 雅人  日本癌学会総会記事  72回-  64  -64  2013/10   [Not refereed] [Not invited]
  • 放射線照射後の乳癌再発に関わるシグナルの解析(Possible mechanisms of non-invasive to invasive phenotypic conversion of breast cancer cells upon radiation)
    南 ジンミン, 小野寺 康仁, 石川 正純, 佐邊 壽孝, 白土 博樹  日本癌学会総会記事  72回-  219  -219  2013/10   [Not refereed] [Not invited]
  • 細胞が持つリサイクルシステム研究の新展開 p53変異によるGEP100-Arf6-AMAP1経路の活性化と乳癌の浸潤形質獲得
    橋本 茂, 橋本 あり, 小根山 千歳, 吉河 歩, 杉野 弘和, 半田 悠, 芳野 正修, 大塚 勇太郎, 小野寺 康仁, 岡田 雅人, 佐邊 壽孝  日本生化学会大会プログラム・講演要旨集  86回-  2S04a  -3  2013/09   [Not refereed] [Not invited]
  • 細胞骨格・細胞運動・細胞移動 GBF1のSec7ドメインのHomology Downstreamは、化学走化性とスーパーオキシド産生に重要な役割を果たすArf活性を持つGPCRシグナル伝達とリンクするホスファチジルイノシトールリン酸と結合する(Cytoskeleton/Cell motility/Cell migration The Homology Downstream of Sec7 domain of GBF1 binds to phosphatidyl inositol phosphates to
    真崎 雄一, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  63回-  116  -116  2011/05   [Not refereed] [Not invited]
  • 橋本茂, 橋本あり, 小根山千歳, 吉河歩, 杉野弘和, 半田悠, 芳野正修, 大塚勇太郎, 小野寺康仁, 岡田雅人, 佐邊壽孝  日本生化学会大会(Web)  86th-  2S04A-3 (WEB ONLY)  2013   [Not refereed] [Not invited]
  • 癌の悪性化における糖代謝と小胞輸送の役割(Glucose metabolism and intracellular trafficking in tumor malignancy)
    小野寺 康仁, 南 ジンミン, 橋本 茂, 橋本 あり, 佐邊 壽孝, Bissell Mina  日本細胞生物学会大会講演要旨集  63回-  119  -119  2011/05   [Not refereed] [Not invited]
  • EphA2によるShp2のチロシンリン酸化はRAS/MAPK経路の持続的活性化に寄与する(Tyrosine phosphorylation of Shp2 by EphA2 contribute to sustained activation of Ras/MAPK pathway)
    三浦 浩一, 若山 勇紀, 佐邊 壽孝, 望月 直樹  日本細胞生物学会大会講演要旨集  63回-  120  -120  2011/05   [Not refereed] [Not invited]
  • TGFβ1による癌的EMTにおけるGEP100-Arf6-AMAP1シグナルの機能解析(HGFR/c-Met-mediated activation of GEP100-Arf6-AMAP1 pathway is an integral part for TGFβ-induced cancerous EMT and invasiveness)
    橋本 あり, 橋本 茂, 大塚 勇太郎, 佐藤 宏紀, 杉野 弘和, 吉河 歩, 梅本 勉, 小野寺 康仁, 福田 諭, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  63回-  151  -151  2011/05   [Not refereed] [Not invited]
  • ephrinA1-EphA2シグナルによるezrinの不活性化とMDCK細胞の形態制御(Inactivation of Ezrin by ephrinA1-EphA2 signaling via RhoA contributes to compaction and polarization of MDCK cells)
    若山 勇紀, 三浦 浩一, 佐邊 壽孝, 望月 直樹  日本細胞生物学会大会講演要旨集  63回-  155  -155  2011/05   [Not refereed] [Not invited]
  • 橋本茂, 橋本あり, 小野寺康仁, 梅本勉, 佐藤宏紀, 毛受暁史, 伊達洋至, 福田諭, 佐邊壽孝  生化学  83回・33回-  ROMBUNNO.3T4-10  -10  2010/12   [Not refereed] [Not invited]
  • EZH2によるmiR-203発現抑制が乳癌浸潤に中枢的であるArf6-AMAP1経路創出に関わる(EZH2-mediated downregulation of miR-203 generates the Arf6-AMAP1 pathway pivotal for breast cancer invasiveness)
    杉野 弘和, 橋本 茂, 橋本 あり, 吉河 歩, 半田 悠, 佐邊 壽孝  日本癌学会総会記事  71回-  87  -87  2012/08   [Not refereed] [Not invited]
  • 橋本あり, 橋本茂, 吉河歩, 杉野弘和, 半田悠, 木下留美子, 畑中佳奈子, 三上修治, 谷野美智枝, 味藤静, 佐藤宏紀, 大塚勇太郎, 芳野日南子, 加戸由加里, NAM Jin‐Min, 小野寺康仁, 田中伸哉, 白土博樹, 佐邊壽孝  日本分子生物学会年会プログラム・要旨集(Web)  35th-  2W10II-1 (WEB ONLY)  2012   [Not refereed] [Not invited]
  • がんの浸潤・転移に関与するGEP100-Arf6-AMAP1経路とc-Metシグナルとの相互作用(GAB1 links c-Met signaling with GEP100-Arf6-AMAP1 pathway to promote breast cancer invasiveness)
    吉河 歩, 橋本 茂, 橋本 あり, 杉野 弘和, 大塚 勇太郎, 味藤 静, 半田 悠, 佐邊 壽孝  日本癌学会総会記事  71回-  87  -87  2012/08   [Not refereed] [Not invited]
  • 乳がん Arf6経路が変異p53とTGFbeta1シグナルに応答して癌的EMTを引き起こす(Topics of breast cancer RTKs-GEP100-Arf6-AMAP1 pathway mediates cancerous EMT in response to mutant p53 and TGFbeta1 signaling)
    佐邊 壽孝  日本癌学会総会記事  71回-  267  -267  2012/08   [Not refereed] [Not invited]
  • 橋本茂, 杉野弘和, 橋本あり, 吉河歩, 大塚勇太郎, 芳野正修, 半田悠, 佐邊壽孝  日本分子生物学会年会プログラム・要旨集(Web)  35th-  2P-0166 (WEB ONLY)  2012   [Not refereed] [Not invited]
  • 非浸潤性乳管癌の3次元培養細胞モデルにおける放射線の影響と再発に関わる分子機序の解析(Targeting integrin suppresses invasive recurrence in a 3D model of radiation treated ductal carcinoma in situ)
    南 ジンミン, Kazi Ahmed, Sylvain Costes, Hui Zhang, 佐邊 壽孝, 白土 博樹, Catherine Park  日本癌学会総会記事  71回-  375  -375  2012/08   [Not refereed] [Not invited]
  • 乳癌浸潤に中枢的なArf6経路は変異p53により創出される(Mutant-p53 generates GEP100-Arf6-AMAP1 pathway to promote breast cancer cell invasiveness in response to TGFbeta1)
    橋本 あり, 橋本 茂, 吉河 歩, 杉野 弘和, 半田 悠, 味藤 静, 佐藤 宏紀, 大塚 勇太郎, 芳野 日南子, 南 ジンミン, 小野寺 康仁, 佐邊 壽孝  日本癌学会総会記事  71回-  399  -399  2012/08   [Not refereed] [Not invited]
  • 癌浸潤におけるAMAP1-PRKD2複合体によるインテグリンリサイクリングとその制御機構(beta1 integrin recycling via AMAP1-PRKD2 complex regulated by small GTPases in cancer invasion)
    小野寺 康仁, 南 ジンミン, 橋本 あり, 白土 博樹, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  71回-  421  -421  2012/08   [Not refereed] [Not invited]
  • 森重真毅, 橋本茂, 阿部竜也, 藤木稔, 古林秀則, 佐邊壽孝  日本脳神経外科学会総会抄録集(CD-ROM)  66th-  2K-P42-12-3  -P42  2007/10   [Not refereed] [Not invited]
  • Fbx8によるユビキチン化を介するArf6の抑制的制御と上皮組織形態形成との関連の可能性について(Fbx8 makes Arf6 refractory to function via ubiquitination: implication in epithelial tissue organization)
    矢野 元, 小野寺 康仁, 鳥井 郁子, 真崎 雄一, 橋本 茂, 辻村 亨, 佐邊 壽孝  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  80回・30回-  1T21  -3  2007/11   [Not refereed] [Not invited]
  • 真崎雄一, 佐邊壽孝  生化学  80回・30回-  2P-0421  -15  2007/11   [Not refereed] [Not invited]
  • EGF刺激による乳癌細胞浸潤におけるAMAP1の詳細な作用機構(AMAP1 promotes β1 integrin recycling via PRKD2 and Rab5c in EGF-induced invasion of breast cancer cells)
    小野寺 康仁, 南 ジンミン, 橋本 茂, 橋本 あり, 白土 博樹, 佐邊 壽孝  日本癌学会総会記事  70回-  37  -38  2011/09   [Not refereed] [Not invited]
  • 変異p53はArf6活性化経路を介した浸潤獲得形質に必須である(Mutant p53 is essential for TGFβ1-induced breast cancer cell invasiveness via activation of GEP100-Arf6-AMAP1 pathway)
    橋本 あり, 橋本 茂, 大塚 勇太郎, 吉河 歩, 杉野 弘和, 半田 悠, 南 ジンミン, 佐藤 宏紀, 福田 諭, 小野寺 康仁, 佐邊 壽孝  日本癌学会総会記事  70回-  38  -38  2011/09   [Not refereed] [Not invited]
  • TGFβ及び低酸素によるArf6活性化を介した癌浸潤形質獲得におけるエピジェネティック因子の関与(EZH2 is essential to Arf6 activation necessary for TGFβ1- and hypoxia-induced invasiveness of breast cancer cells)
    橋本 茂, 橋本 あり, 小野寺 康仁, 大塚 勇太郎, 吉河 歩, 杉野 弘和, 半田 悠, 佐藤 宏紀, 福田 諭, 毛受 暁史, 佐邊 壽孝  日本癌学会総会記事  70回-  77  -77  2011/09   [Not refereed] [Not invited]
  • TGFβ1はGEP100-Arf6-AMAP1経路の活性化によりEMTを誘導し、この活性化は癌幹細胞性と関連する(TGFβ1 activates GEP100-Arf6-AMAP1 pathway to induce EMT, and possible relationship of this activation to cancer stemness)
    橋本 あり, 平野 真理子, 谷野 美智枝, 梅本 勉, 小野寺 康仁, 佐藤 宏紀, 木下 留美子, 南 ジンミン, 大塚 勇太郎, 福田 諭, 白土 博樹, 相沢 慎一, 橋本 茂, 田中 伸哉, 佐邊 壽孝  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  83回・33回-  2P  -0237  2010/12   [Not refereed] [Not invited]
  • 過剰発現したHer2/Neu/ErbB2とGEP100/BRAG2の連係は肺腺癌の自律的な浸潤活性を誘導し、転移を予測するバイオマーカーを提供する(Engagement of GEP100/BRAG2 with overexpressed Her2/Neu/ErbB2 induces autonomous invasive activities and provides a biomarker predictive for metastases of lung adenocarcinoma)
    毛受 暁史, 橋本 茂, 橋本 あり, 伊達 洋至, 佐邊 壽孝  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  83回・33回-  2P  -0238  2010/12   [Not refereed] [Not invited]
  • 癌の悪性化における小胞輸送と糖代謝の役割(Intracellular trafficking and glucose metabolism in tumor malignancy)
    小野寺 康仁, 佐邊 壽孝  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  83回・33回-  3P  -1019  2010/12   [Not refereed] [Not invited]
  • 癌の悪性化における小胞輸送と糖代謝の役割(Roles of intracellular trafficking and glucose metabolism in tumor malignancy)
    小野寺 康仁, 佐邊 壽孝  日本癌学会総会記事  69回-  83  -83  2010/08   [Not refereed] [Not invited]
  • 上皮間葉転換 Arf6-AMAP1経路は癌的EMTに寄与する(EMT (Epithelial Mesenchymal Transition) The Arf6-AMAP1 pathway contributes to cancerous EMT)
    佐邊 壽孝, 小野寺 康仁, 橋本 あり, 橋本 茂  日本癌学会総会記事  69回-  240  -240  2010/08   [Not refereed] [Not invited]
  • SABE Hisataka  生化学  74-  (12)  1429  -1440  2002/12   [Not refereed] [Not invited]  
    細胞運動は細胞の接着,前方部の伸展,核を含めた細胞体の牽引,後方部の脱接着,細胞体の前方への移動の少なくとも五つのレパートリーからなり,それらは細胞内の物理力の発生や運動方向極性の決定機序などとも統制され,時空間的な順序をもっておこる.物理力や極性発生の機構も互いに提携し統制され,その結果,意味のある効率的な運動がなされる.細胞内シグナル伝達,細胞骨格再構成,膜の細胞内輸送や再構成などの各々個別の過程が,これらの機序や機構を作動させる.現在の細胞生物学における重要な問題点の一つはこれら個別の細胞内過程を互いに調整し統制している機構の分子的実態を明らかにすることである
  • HER2はGEP100を介して肺癌の浸潤転移を促進する(ErbB2/Her2/Neu employs GEP100 to promote lung cancer invasion and metastasis)
    毛受 暁史, 橋本 茂, 橋本 あり, 伊達 洋至, 佐邊 壽孝  日本癌学会総会記事  69回-  266  -266  2010/08   [Not refereed] [Not invited]
  • 低酸素下の癌細胞の浸潤形質獲得とArf6活性化との関連(Hypoxia-induced invasive activity of breast cancer cells involves Arf6 activation)
    橋本 茂, 橋本 あり, 小野寺 康仁, 梅本 勉, 佐藤 宏紀, 毛受 暁史, 佐邊 壽孝  日本癌学会総会記事  69回-  418  -419  2010/08   [Not refereed] [Not invited]
  • TGFβによって誘導される癌的EMTにおけるGEP100-Arf6-AMAP1シグナルとHGFRとの相互作用(HGFR-mediated GEP100-Arf6-AMAP1 pathway is an integral part for TGFβ-induced cancerous EMT and invasiveness)
    橋本 あり, 平野 真理子, 梅本 勉, 小野寺 康仁, 佐藤 宏紀, 大塚 勇太郎, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  69回-  419  -419  2010/08   [Not refereed] [Not invited]
  • がん増殖を解くシグナル伝達研究の新展開 癌の悪性化における小胞輸送と糖代謝の役割(New frontiers of signal transduction toward understanding cancer growth Intracellular traffic and glucose metabolism in tumor malignancy)
    小野寺 康仁, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  62回-  105  -105  2010/05   [Not refereed] [Not invited]
  • シグナル伝達 EphA2によるリガンド非依存的なRas/MAPK経路の活性化機構(Signal transduction Ligand-independent role of EphA2 in activation of the Ras/MAPK pathway)
    三浦 浩一, 若山 勇紀, 佐邊 壽孝, 望月 直樹  日本細胞生物学会大会講演要旨集  62回-  113  -113  2010/05   [Not refereed] [Not invited]
  • 細胞運動・ECM・細胞接着 Zyxinは上皮間葉転換においてアクチン線維再編成に関与し心内膜床の形態形成に寄与する(Cell motility, ECM and cell adhesion Zyxin Mediates Actin Fiber Reorganization in Epithelial-Mesenchymal Transition and Contributes to Endocardial Morphogenesis)
    森 雅樹, 中神 啓徳, 鯉渕 信孝, 三浦 浩一, 佐邊 壽孝, 望月 直樹, 金田 安史  日本細胞生物学会大会講演要旨集  62回-  120  -120  2010/05   [Not refereed] [Not invited]
  • 好中球においてゴルジ体に局在するArfGEFのPI3Kγによる局在変化と活性化は、GPCR刺激と細胞運動を結びつけている(Translocation and activation of a Golgi-localizing ArfGEF via PI3Kγ links GPCR stimulation with directional migration in neutrophils)
    真崎 雄一, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  62回-  138  -138  2010/05   [Not refereed] [Not invited]
  • Arf6を介したephrinA1-EphA2シグナルによるEzrinの不活性化はMDCK細胞の形態変化に寄与する(Inactivation of Ezrin by ephrinA1-EphA2 signaling via Arf6 contributes to compaction of MDCK cells)
    若山 勇紀, 三浦 浩一, 佐邊 壽孝, 望月 直樹  日本細胞生物学会大会講演要旨集  62回-  141  -141  2010/05   [Not refereed] [Not invited]
  • GEP100-Arf6-AMAP1経路は癌浸潤と血管新生に対する共通の分子標的である(GEP100-Arf6-AMAP1 pathway is activated by VEGFR2 and promotes vascular remodeling and VE-cadherin endocytosis in endothelial cells)
    橋本 あり, 橋本 茂, 小川 栄治, 毛受 暁史, 森重 真毅, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  62回-  161  -161  2010/05   [Not refereed] [Not invited]
  • 癌の転移部における休止と再発 EMTから考える
    佐邊 壽孝  日本細胞生物学会大会講演要旨集  62回-  215  -215  2010/05   [Not refereed] [Not invited]
  • 佐邊壽孝  がん研究に係わる特定領域研究研究報告集録 平成21年度  197  2010   [Not refereed] [Not invited]
  • 佐邊壽孝  生化学  ROMBUNNO.3S1A-2  2009/09   [Not refereed] [Not invited]
  • 低分子量GTPaseから眺めるメンブレントラフィック研究の新展開 メンブレントラフィックと癌浸潤形質獲得機序
    佐邊 壽孝  日本生化学会大会プログラム・講演要旨集  82回-  3S1a  -2  2009/09   [Not refereed] [Not invited]
  • EphA2受容体によるArf6の不活性化と上皮細胞間の接着制御(EphA2 engages Git1 to suppress Arf6 activity and modulate epithelial cell-cell contacts)
    三浦 浩一, Nam Jin-Min, 児島 千恵, 望月 直樹, 佐邊 壽孝  日本生化学会大会プログラム・講演要旨集  82回-  2T15p  -10  2009/09   [Not refereed] [Not invited]
  • 乳癌細胞における恒常的なNF-kappaBの活性化に対するNIKおよびA20の役割(Roles for NIK and A20 in constitutive NF-kappaB activation in breast cancer cells)
    斉藤 愛記, 橋本 茂, 佐邊 壽孝, 山岡 昇司  日本癌学会総会記事  68回-  323  -323  2009/08   [Not refereed] [Not invited]
  • セマフォリンシグナル伝達とエフリンシグナル伝達に関する最新の知見 上皮細胞間接触を制御するArf6のGit1による抑制におけるEphA2の関与(Recent advances in semaphorin signaling and ephrin signaling EphA2 engages Git1 to suppress Arf6 activity modulating epithelial cell-cell contacts)
    三浦 浩一, Nam Jin-Min, 児島 千恵, 望月 直樹, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  61回-  112  -112  2009/05   [Not refereed] [Not invited]
  • 好中球のケモタキシスにおけるGBF1の役割(Roles of GBF1 in neutrophil chemotaxis)
    真崎 雄一, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  61回-  148  -148  2009/05   [Not refereed] [Not invited]
  • 佐邊壽孝  がん研究に係わる特定領域研究研究報告集録 平成20年度  201  2009   [Not refereed] [Not invited]
  • 佐邊壽孝  がん特定研究5領域合同シンポジウムプログラム・抄録集 平成20年度  12  2009   [Not refereed] [Not invited]
  • 蛋白質のリン酸化と細胞応答 GEP100-Arf6-AMAP1-cortactinシグナル経路は癌浸潤と血管新生に共通である
    橋本 あり, 橋本 茂, 小川 栄治, 廣瀬 まゆみ, 森重 真毅, 毛受 暁史, 小野寺 康仁, 渋谷 正史, 佐邊 壽孝  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  81回・31回-  4S2  -3  2008/11   [Not refereed] [Not invited]
  • 濃度勾配性因子による細胞極性・細胞運動の制御 組織構築、創傷治癒およびがんの浸潤・転移の機構解明を目指して 乳癌浸潤転移におけるEGFR-GEP100-Arf6-AMAP1経路 微小環境との相互作用
    佐邊 壽孝, 橋本 茂, 森重 真毅, 橋本 あり, 小川 栄二, 矢野 元, Nam Jinmin, 小野寺 康仁  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  81回・31回-  4S14  -3  2008/11   [Not refereed] [Not invited]
  • 橋本茂, 森重真毅, 小川栄治, 橋本あり, 小野寺康仁, 佐邊壽孝  実験医学  26-  (15)  2349  -2355  2008/09   [Not refereed] [Not invited]
  • 【シグナル伝達研究 2008'09 疾患発症の分子メカニズムと実現化する分子標的薬開発】 シグナル伝達研究 因子から現象へ がんの浸潤形質獲得過程における低分子量Gタンパク質Arf6シグナル伝達
    橋本 茂, 森重 真毅, 小川 栄治, 橋本 あり, 小野寺 康仁, 佐邊 壽孝  実験医学  26-  (15)  2349  -2355  2008/09   [Not refereed] [Not invited]  
    がんの主たる脅威は、浸潤・転移性の獲得にある。恒常性を維持した細胞浸潤は、胎児期の発生・分化過程や創傷治癒、免疫応答などでみられるが、どのような制御機構の破綻ががんの浸潤形質を誘導しているのか未だ不明のままである。がんの浸潤形質獲得は、がん細胞自身のgenetic/epigeneticな変異の多段階的蓄積のみならず、微小環境の変化に依存している。われわれは、低分子量Gタンパク質Arf6を中心としたシグナル伝達経路の活性化が浸潤形質の獲得に必須であることを見出した。本稿では、がん浸潤形質の誘導に関連した最近の知見を概説するとともに、われわれのモデルについて紹介したい。(著者抄録)
  • 低酸素環境とEMTにおける乳腺上皮細胞の浸潤性獲得に関連する網羅的解析(Comprehensive analysis for the acquisition of invasiveness of mammary epithelial cells under hypoxia and EMT)
    橋本 茂, 橋本 あり, 魏 樹梅, 三浦 浩一, 毛受 暁史, 佐邊 壽孝  日本癌学会総会記事  67回-  101  -101  2008/09   [Not refereed] [Not invited]
  • GEP100-Arf6経路は血管新生と癌浸潤に共通のシグナル経路である(Common usage of the GEP100-Arf6 signaling pathway in tumor invasion, angiogenesis, and vascular permeability)
    橋本 あり, 橋本 茂, 小川 栄治, 廣瀬 まゆみ, 森重 真毅, 毛受 暁史, 渋谷 正史, 佐邊 壽孝  日本癌学会総会記事  67回-  296  -296  2008/09   [Not refereed] [Not invited]
  • 癌浸潤転移における細胞運動のメカニズム 血管新生と癌浸潤に共通なシグナル経路(Molecular mechanisms of cell migration in cancer invasion and metastasis Common usage of an Arf6-GEP100 signaling pathway in angiogenesis and tumor invasion)
    橋本 あり, 橋本 茂, 小川 栄治, 廣瀬 まゆみ, 高島 成二, 森重 真毅, 毛受 暁史, 南 ジンミン, 真崎 雄一, 北風 政史, 渋谷 正史, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  60回-  95  -95  2008/06   [Not refereed] [Not invited]
  • 橋本あり, 橋本茂, 小川栄治, 廣瀬まゆみ, 森重真毅, 毛受暁史, 小野寺康仁, 渋谷正史, 佐邊壽孝  生化学  4S2-3  2008   [Not refereed] [Not invited]
  • 佐邊壽孝, 橋本茂, 森重真毅, 橋本あり, 小川栄二, 矢野元, NAM Jinmin, 小野寺康仁  生化学  4S14-3  2008   [Not refereed] [Not invited]
  • 橋本茂, 三浦浩一, 橋本あり, WEI Shumei, 毛受暁史, 佐邊壽孝  生化学  2P-0426  2008   [Not refereed] [Not invited]
  • 佐邊壽孝  がん研究に係わる特定領域研究研究報告集録 平成19年度  216  2008   [Not refereed] [Not invited]
  • EGFレセプターシグナルを介した乳癌細胞の浸潤形質誘導における必須因子Arf6の活性化機序(GEP100 links epidermal growth factor receptor signaling to Arf6 activation to induce breast cancer invasion)
    橋本 茂, 森重 真毅, 小川 栄治, 廣瀬 まゆみ, 魏 樹梅, 橋本 あり, 山田 敦子, 矢野 元, 仁尾 義則, 和田 洋巳, 古林 秀則, 佐邊 壽孝  日本癌学会総会記事  66回-  58  -58  2007/08   [Not refereed] [Not invited]
  • Git1は、Arf6活性化E-cadherin誘発細胞接着を抑制するために、Nckを介してリガンド活性化EphA2と結合する(Git1 links to ligand-activated EphA2 via Nck to suppress Arf6 activity modulatinq E-cadherin-mediated cell-cell contacts)
    三浦 浩一, Nam Jin-Min, 佐邊 壽孝  日本癌学会総会記事  66回-  132  -132  2007/08   [Not refereed] [Not invited]
  • 癌浸潤及び血管新生におけるArf6活性化の意義(Common usage of Arf6-signaling pathway in tumor invasion and angiogenesis)
    橋本 あり, 南 ジンミン, 森重 真毅, 毛受 暁史, 橋本 茂, 渋谷 正史, 佐邊 壽孝  日本癌学会総会記事  66回-  142  -142  2007/08   [Not refereed] [Not invited]
  • Arf6をユビキチン化するE3リガーゼFbx8のがんにおける発現不全(Loss of Fbx8, a component of E3 ligase mediating Arf6 ubiquitination, in different human tumors)
    矢野 元, 真崎 雄一, 橋本 茂, 辻村 亨, 佐邊 壽孝  日本癌学会総会記事  66回-  142  -143  2007/08   [Not refereed] [Not invited]
  • EMT進行と細胞移動における赤血球タンパク質band4.1-like5(Ebl5)の重要な役割(Erythrocyte protein band4.1-like5 (Ebl5) plays an essential role in the EMT progression and cell migration)
    平野 真理子, 佐邊 壽孝, 相澤 慎一  日本発生生物学会・日本細胞生物学会合同大会要旨集  40回・59回-  169  -169  2007/05   [Not refereed] [Not invited]
  • 平野真理子, 佐邊壽孝, 相澤慎一  生化学  3P-1004  2007   [Not refereed] [Not invited]
  • 佐邊壽孝  がん研究に係わる特定領域研究研究報告集録 平成18年度  216  2007   [Not refereed] [Not invited]
  • 宮田真理子, ANTONIS Koromilas, 佐邊壽孝  生化学  3P-0641  2007   [Not refereed] [Not invited]
  • Eph受容体によるE-カドヘリンを介した細胞間接着の制御
    三浦 浩一, 佐邊 壽孝  日本癌学会総会記事  65回-  241  -241  2006/09   [Not refereed] [Not invited]
  • 乳癌細胞の浸潤におけるAMAP1のユビキチン化の役割(Property of AMAP1 to be monoubiquitinated via binding with CIN85 and Cbl is crucial for breast cancer invasive activity)
    Nam Jin-Min, 小野寺 康仁, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  65回-  295  -296  2006/09   [Not refereed] [Not invited]
  • 乳癌細胞におけるFbox8発現不全と浸潤性獲得の関連性
    矢野 元, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  65回-  296  -296  2006/09   [Not refereed] [Not invited]
  • AMAP1/コータクチン複合体形成阻害による血管新生及びmesenchymal型とamoeboid型癌浸潤の阻害
    橋本 あり, 山田 敦子, 森重 真毅, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  65回-  311  -311  2006/09   [Not refereed] [Not invited]
  • 乳癌細胞の浸潤形質獲得における必須因子Arf6の活性化機序
    橋本 茂, 森重 真毅, 古林 秀則, 橋本 あり, 魏 樹梅, 山田 敦子, 佐邊 壽孝  日本癌学会総会記事  65回-  456  -456  2006/09   [Not refereed] [Not invited]
  • 三浦浩一, 佐邊壽孝  日本癌学会学術総会記事  65th-  241  2006/08   [Not refereed] [Not invited]
  • 矢野元, 橋本茂, 佐邊壽孝  日本癌学会学術総会記事  65th-  296  2006/08   [Not refereed] [Not invited]
  • 橋本茂, 森重真毅, 古林秀則, 橋本あり, WEI Shumei, 山田敦子, 佐邊壽孝  日本癌学会学術総会記事  65th-  456  2006/08   [Not refereed] [Not invited]
  • 橋本あり, 山田敦子, 森重真毅, 橋本茂, 佐邊壽孝  日本癌学会学術総会記事  65th-  311  2006/08   [Not refereed] [Not invited]
  • 小野寺康仁, 佐邊壽孝  実験医学  24-  (10)  1433  -1439  2006/06   [Not refereed] [Not invited]
  • 【分子メカニズムから解き明かす疾患のサイエンス】 癌 癌細胞の浸潤・転移におけるタンパク質の相互作用と動態の制御
    小野寺 康仁, 佐邊 壽孝  実験医学  24-  (10)  1433  -1439  2006/06   [Not refereed] [Not invited]  
    癌の転移において癌細胞の浸潤活性は最も重要な性質の1つである.癌細胞は,既存分子の相互作用を改変して細胞-細胞間接着や細胞-基質間接着,運動性や細胞外基質分解活性を巧みに制御し,浸潤・転移を行うものと考えられる.これらの過程に特異的に関与するタンパク質間相互作用の同定は,正常組織への副作用を抑えた浸潤・転移阻害薬の開発において有効な情報を与えることが期待される(著者抄録)
  • 廣瀬まゆみ, 橋本茂, 橋本あり, 森重真毅, 山田敦子, 保坂晴美, 赤木謙一, 小川栄治, 池上貴久, 中川敦史, 佐邊壽孝  日本蛋白質科学会年会プログラム・要旨集  6th-  67  2006/03   [Not refereed] [Not invited]
  • 佐邊壽孝  Arf6による細胞運動性制御の分子機構の解析 平成16-17年度 No.16370090  97P  2006   [Not refereed] [Not invited]
  • ヒト単球芽様細胞U937の分化におけるAMAP1蛋白質量の上昇機構の解析
    宮田 真理子, 佐邊 壽孝  日本免疫学会総会・学術集会記録  35-  54  -54  2005/11   [Not refereed] [Not invited]
  • 細胞間接触によるArf6の負の制御
    三浦 浩一, 小野寺 康仁, 佐邊 壽孝  日本癌学会総会記事  64回-  167  -167  2005/09   [Not refereed] [Not invited]
  • Arf6ユビキチン化機構と乳癌細胞浸潤性獲得過程との関連性
    矢野 元, 橋本 茂, 小野寺 康仁, 佐邊 壽孝  日本癌学会総会記事  64回-  173  -173  2005/09   [Not refereed] [Not invited]
  • 浸潤性乳癌細胞のAMAP1/コータクチン相互作用インターフェースの癌浸潤阻害剤の標的としての評価
    橋本 茂, 廣瀬 まゆみ, 橋本 あり, 森重 真毅, 山田 敦子, 小野寺 康仁, 小川 栄治, 和田 洋巳, 池上 貴久, 中川 敦史, 佐邊 壽孝  日本癌学会総会記事  64回-  309  -309  2005/09   [Not refereed] [Not invited]
  • 浸潤・転移・血管新生研究の進歩 乳癌における浸潤形質獲得過程
    佐邊 壽孝, 小野寺 康仁, ナム・ジンミン, 橋本 あり, 森重 真毅, 橋本 茂  日本癌学会総会記事  64回-  513  -513  2005/09   [Not refereed] [Not invited]
  • 【発生・分化再生研究2005】 形態形成 細胞間相互作用とシグナル伝達 上皮細胞における接着分子機能の動的制御
    三浦 浩一, 佐邊 壽孝  実験医学  23-  (1)  46  -51  2005/01   [Not refereed] [Not invited]
  • 乳癌の浸潤活性におけるArf6の要求性
    佐邊 壽孝  上原記念生命科学財団研究報告集  18-  203  -205  2004/11   [Not refereed] [Not invited]  
    低分子量G蛋白質Arf6(ADP-ribosylation factor 6)活性とその発現レベルと乳癌浸潤性との関係について検討した.MDA-MB-231細胞をはじめとする種々のヒト乳癌細胞株は全てATCCより入手した.siRNAは常法により施行した.Arf6は乳癌におけるinvadopodiaの一要素で,siRNA法によってArf6の発現を抑制すると乳癌の浸潤活性を効率良く阻害できた.mRNAは培養された正常乳腺上皮細胞でもすでに発現し,浸潤性とは相関していなかった.種々のcDNAや方法論を用いて解析したところ,Arf6の持続的活性化が乳癌の浸潤活性に必須であることが示唆された
  • がんの微小環境制御による浸潤・転移治療を目指して 乳癌の浸潤性獲得 隠された浸潤装置
    佐邊 壽孝  日本癌学会総会記事  63回-  391  -391  2004/09   [Not refereed] [Not invited]
  • 乳癌細胞におけるArf6蛋白質の量的制御機構と浸潤性獲得
    矢野 元, 古林 格, 小野寺 康仁, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  63回-  265  -265  2004/09   [Not refereed] [Not invited]
  • Arf6は乳癌細胞の浸潤性獲得において必須の分子装置の一つである
    橋本 茂, 小野寺 康仁, 橋本 あり, 森重 真毅, 田中 美和, 浜口 道成, 佐邊 壽孝  日本癌学会総会記事  63回-  265  -265  2004/09   [Not refereed] [Not invited]
  • 浸潤性乳癌細胞におけるAMAP1の発現と機能
    小野寺 康仁, 橋本 茂, 真崎 雄一, 橋本 あり, 森重 真毅, 松浦 成昭, 佐邊 壽孝  日本癌学会総会記事  63回-  267  -267  2004/09   [Not refereed] [Not invited]
  • 皮膚線維芽細胞におけるUltraviolet A照射によるマトリックスメタロプロテアーゼ1の発現はMacrophage migration inhibitory factorを介する
    渡辺 宏数, 清水 忠道, 西平 順, 阿部 理一郎, 中山 敏則, 谷口 克, 佐邊 壽孝, 石橋 輝雄, 清水 宏  生化学  75-  (12)  1570  -1570  2003/12   [Not refereed] [Not invited]
  • 医学・医療の進歩を世界へ向けて 細胞内情報伝達・分子細胞医学 細胞の接着・形態形成と細胞内情報伝達 Endosomal Recyclingと細胞運動性制御
    佐邊 壽孝  日本医学会総会会誌  26回-  (2)  210  -210  2003/12   [Not refereed] [Not invited]
  • カドヘリン接着形成におけるインテグリンシグナル分子群の役割
    矢野 元, 真崎 雄一, 三浦 浩一, 佐邊 壽孝  日本癌学会総会記事  62回-  40  -40  2003/08   [Not refereed] [Not invited]
  • 低分子量G蛋白質Ralの下流分子であるPOB1は,パキシリン結合蛋白質PAG2と結合し,細胞運動を制御する
    大城 望史, 小山 眞也, 杉山 真一郎, 佐邊 壽孝, 菊池 章  生化学  74-  (8)  1049  -1049  2002/08   [Not refereed] [Not invited]
  • 細胞外マトリックス系による細胞増殖と機能の制御 運動中の細胞における,パキシリンのチロシン31及び118のリン酸化により制御されるRhoA活性抑制の局在化機構
    坪内 朝子, 坂倉 純子, 八木 良平, 真崎 雄一, Schaefer Erik, 矢野 元, 佐邊 壽孝  日本発生生物学会大会講演要旨集  35回-  98  -98  2002/05   [Not refereed] [Not invited]
  • Y. Mazaki, S. Hashimoto, K. Okawa, A. Tsubouchi, K. Nakamura, R. Yagi, H. Yano, A. Kondo, A. Iwamatsu, A. Mizoguchi, H. Sabe  Molecular Biology of the Cell  12-  645  -662  2001/11   [Not refereed] [Not invited]  
    Paxillin acts as an adaptor protein in integrin signaling. We have shown that paxillin exists in a relatively large cytoplasmic pool, including perinuclear areas, in addition to focal complexes formed at the cell periphery and focal adhesions formed underneath the cell. Several ADP-ribosylation factor (ARF) GTPase-activating proteins (GAPs; ARFGAPs) have been shown to associate with paxillin. We report here that Git2-short/KIAA0148 exhibits properties of a paxillin-associated ARFGAP and appears to be colocalized with paxillin, primarily at perinuclear areas. A fraction of Git2-short was also localized to actin-rich structures at the cell periphery. Unlike paxillin, however, Git2-short did not accumulate at focal adhesions underneath the cell. Git2-short is a short isoform of Git2, which is highly homologous to p95PKL, another paxillin-binding protein, and showed a weaker binding affinity toward paxillin than that of Git2. The ARFGAP activities of Git2 and Git2-short have been previously demonstrated in vitro, and we provided evidence that at least one ARF isoform, ARF1, is an intracellular substrate for the GAP activity of Git2-short. We also showed that Git2-short could antagonize several known ARF1-mediated phenotypes: overexpression of Git2-short, but not its GAP-inactive mutant, caused the redistribution of Golgi protein β-COP and reduced the amounts of paxillin-containing focal adhesions and actin stress fibers. Perinuclear localization of paxillin, which was sensitive to ARF inactivation, was also affected by Git2-short overexpression. On the other hand, paxillin localization to focal complexes at the cell periphery was unaffected or even augmented by Git2-short overexpression. Therefore, an ARFGAP protein weakly interacting with paxillin, Git2-short, exhibits pleiotropic functions involving the regulation of Golgi organization, actin cytoskeletal organization, and subcellular localization of paxillin, all of which need to be coordinately regulated during integrin-mediated cell adhesion and intracellular signaling.
  • 癌細胞の浸潤におけるパキシリンのチロシンリン酸化の役割
    岩崎 輝夫, 向井 睦子, 矢野 元, 佐邊 壽孝, 杉原 綾子, 山田 直子, 辻村 亨, 寺田 信行  日本病理学会会誌  91-  (1)  197  -197  2002/03   [Not refereed] [Not invited]
  • Ralの下流分子であるPOB1とARF-GAPとの結合による細胞運動の制御
    大城 望史, 小山 眞也, 近藤 明子, 佐邊 壽孝, 菊池 章  生化学  73-  (8)  811  -811  2001/08   [Not refereed] [Not invited]
  • 上皮細胞運動におけるPyk2とFakの活性制御とシグナル伝達の解析
    矢野 元, 中村 邦明, Schaefer Erik, 佐邊 壽孝  生化学  73-  (8)  811  -811  2001/08   [Not refereed] [Not invited]
  • 細胞接着分子研究の進歩 細胞運動における細胞骨格再構成と形質膜再構成との統御機構
    佐邊 壽孝  炎症・再生  21-  (4)  443  -443  2001/07   [Not refereed] [Not invited]
  • ダイナミックな細胞骨格制御と細胞機能 パキシリン結合性ARFGAP蛋白質のアクチン細胞骨格制御における役割
    真崎 雄一, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  54回-  3  -3  2001/05   [Not refereed] [Not invited]
  • Hiroshi Uchida, Hiroshi Uchida, Akiko Kondo, Yasunori Yoshimura, Yuichi Mazaki, Hisataka Sabe, Hisataka Sabe, Hisataka Sabe  Journal of Experimental Medicine  193-  955  -966  2001/04   [Not refereed] [Not invited]  
    The Fcγ receptor (FcγR)-mediated phagocytosis of macrophages is a complex process where remodeling of both the actin-based cytoskeleton and plasma membrane occur coordinately. Several different families of small GTPases are involved. We have isolated a GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF), paxillin-associated protein with ARFGAP activity (PAG)3/Papα/KIAA0400, from mature monocytes and macrophage-like cells. Mammalian ARFs fall into three classes, and the class III isoform (ARF6) has been shown to be involved in FcγR-mediated phagocytosis. Here we report that PAG3 is enriched together with ARF6 and F-actin at phagocytic cups formed beneath immunoglobulin G-opsonized beads in P388D1 macrophages, in which overexpression of ARF6, but not ARF1 (class I) or ARF5 (class II), inhibits the phagocytosis. Overexpression of PAG3, but not its GAP-inactive mutant, attenuated the focal accumulation of F-actin and blocked phagocytosis, although surface levels of the FcγRs were not affected. Other ubiquitously expressed ARFGAPs, G protein-coupled receptor kinase interactors GIT2 and GIT2-short/KIAA0148, which we have shown to exhibit GAP activity for ARF1 in COS-7 cells, did not accumulate at the phagocytic cups or inhibit phagocytosis. Moreover, cooverexpression of ARF6, but not ARF1 or ARF5, restored the phagocytic activity of PAG3-overexpressing cells. We propose that PAG3 acts as a GAP for ARF6 and is hence involved in FcγR-mediated phagocytosis in mouse macrophages.
  • マトリックス分子シグナルの多様性と細胞接着 細胞運動制御おけるチロシンリン酸化の役割
    矢野 元, 坪内 朝子, 佐邊 壽孝  日本細胞生物学会大会講演要旨集  54回-  37  -37  2001/05   [Not refereed] [Not invited]
  • Kuniaki Nakamura, Hajime Yano, Hiroshi Uchida, Shigeru Hashimoto, Erik Schaefer, Hisataka Sabe, Hisataka Sabe, Hisataka Sabe, Hisataka Sabe  Journal of Biological Chemistry  275-  27155  -27164  2000/09   [Not refereed] [Not invited]  
    Temporal and spatial regulation of actin-based cytoskeletal organization and focal adhesion formation play an essential role in cell migration. Here, we show that tyrosine phosphorylation of a focal adhesion protein, paxillin, crucially participates in these regulations. We found that tyrosine phosphorylation of paxillin was a prominent event upon integrin activation during epithelial-mesenchymal trans-differentiation and cell migration. Four major tyrosine phosphorylation sites were identified, and two of them were highly inducible upon integrin activation. Paxillin exhibits three distinct subcellular localizations as follows: localization along the cell periphery colocalized with circumferential actin meshworks, macroaggregation at focal adhesions connected to actin stress fibers, and diffuse cytoplasmic distribution. Tyrosine phosphorylation of paxillin localized at the cell periphery and focal adhesions was shown using phosphorylation site-specific antibodies. Mutations in the phosphorylation sites affected the peripheral localization of paxillin and paxillin-containing focal adhesion formation during cell migration and cell-cell collision, accompanied by altered actin organizations. Our analysis indicates that phosphorylation of multiple tyrosines in paxillin α is necessary for the proper function of paxillin and is involved in the temporospatial regulation of focal adhesion formation and actin cytoskeletal organization in motile cells.
  • パキシリンとp130Casは,そのチロシンリン酸化を介し,細胞運動調節とcontact inhibition of growthにおいて相反的に作用する
    矢野 元, 内田 浩, 岩崎 輝夫, 向井 睦子, 明渡 均, 中村 邦明, 佐邊 壽孝  日本癌学会総会記事  59回-  135  -135  2000/09   [Not refereed] [Not invited]
  • スフィンゴ脂質蓄積症における脳内巨大多核細胞産生機構の解析
    金沢 崇之, 中村 祥子, 桃井 道子, 山地 俊之, 竹松 弘, 矢野 元, 佐邊 壽孝, 山本 章嗣, 川嵜 敏祐, 小堤 保則  生化学  72-  (8)  713  -713  2000/08   [Not refereed] [Not invited]
  • Akiko Kondo, Akiko Kondo, Shigeru Hashimoto, Hajime Yano, Kuniaki Nagayama, Yuichi Mazaki, Hisataka Sabe, Hisataka Sabe, Hisataka Sabe  Molecular Biology of the Cell  11-  1315  -1327  2000/04   [Not refereed] [Not invited]  
    Paxillin acts as an adaptor molecule in integrin signaling. Paxillin is localized to focal contacts but seems to also exist in a relatively large cytoplasmic pool. Here, we report the identification of a new paxillin- binding protein, PAG3 (paxillin-associated protein with ADP-ribosylation factor [ARF] GTPase-activating protein [GAP] activity, number 3), which is involved in regulation of the subcellular localization of paxillin. PAG3 bound to all paxillin isoforms and was induced during monocyte maturation, at which time paxillin expression is also increased and integrins are activated. PAG3 was diffusely distributed in the cytoplasm in premature monocytes but became localized at cell periphery in madre monocytes, a fraction of which then colocalized with paxillin. PAG3, on the other hand, did not accumulate at focal adhesion plaques, suggesting that PAG3 is not an integrin assembly protein. PAG3 was identical to KIAA0400/Papα, which was previously identified as a Pyk2-binding protein bearing a GAP activity toward several ARFs in vitro. Mammalian ARFs fall into three classes, and we showed that all classes could affect subcellular localization of paxillin. We also examined possible interaction of PAG3 with ARFs and showed evidence that at least one of them, ARF6, seems to be an intracellular substrate for GAP activity of PAG3. Moreover, overexpression of PAG3, but not its GAP-inactive mutant, inhibited paxillin recruitment to focal contacts and hampered cell migratory activities, whereas cell adhesion activities were almost unaffected. Therefore, our results demonstrate that paxillin recruitment to focal adhesions is not mediated by simple cytoplasmic diffusion; rather, PAG3 appears to be involved in this process, possibly through its GAP activity toward ARF proteins. Our result thus delineates a new aspect of regulation of cell migratory activities.
  • 細胞接着と細胞骨格の制御と細胞形態形成 細胞骨格制御におけるパキシリンと低分子量G蛋白質群との機能連関
    佐邊 壽孝, 橋本 茂, 近藤 明子, 坪内 朝子, 内田 浩, 中村 邦明, 矢野 元, 真崎 雄一  生化学  72-  (8)  593  -593  2000/08   [Not refereed] [Not invited]
  • Tetsuo Maruyama, Tetsuo Maruyama, Tetsuo Maruyama, Yasunori Yoshimura, Junji Yodoi, Hisataka Sabe, Hisataka Sabe  Endocrinology  140-  2632  -2636  1999/12   [Not refereed] [Not invited]  
    Tyrosine phosphorylation of cellular proteins, controlled coordinately by tyrosine kinases and phosphatases, is a critical element in signal transduction pathways involved in the regulation of biological responses including cell growth and differentiation. Decidualization is a dramatic progesterone-induced differentiation of the estrogen-primed endometrium, which is crucial for embryo implantation and maintenance of pregnancy. Here we have shown that the kinase activity of c-Src was increased, accompanied by altered tyrosine phosphorylation of several cellular proteins, during in vitro decidualization of human endometrial stromal cells. Withdrawal of both estrogen and progesterone from the cultures of decidualized stromal cells reduced c-Src kinase activity to the basal level and also changed the pattern of tyrosine phosphorylation of the several cellular proteins to the unstimulated state. The kinase activity of endometrial c-Src appeared to inversely correlate with the level of its tyrosine phosphorylation. Moreover, although the endometrial stromal cells expressed another src-family kinase, Fyn, the activity of the Fyn kinase was almost undetectable during decidualization and thereafter upon steroid withdrawal. Our findings suggest that the activation of c-Src kinase may be a normal physiological event associated with decidualization, being specifically involved in the signaling cascades mediated by ovarian hormone stimulation.
  • ヒト子宮内膜間質細胞脱落膜化過程における接着斑分子の動態
    丸山 哲夫, 吉村 泰典, 野澤 志朗, 佐邊 壽孝  日本産科婦人科学会雑誌  52-  (2)  334  -334  2000/02   [Not refereed] [Not invited]
  • Tetsuo Maruyama, Tetsuo Maruyama, Tetsuo Maruyama, Tetsuo Maruyama, Yasunori Yoshimura, Hisataka Sabe, Hisataka Sabe  Endocrinology  140-  5982  -5990  1999/12   [Not refereed] [Not invited]  
    Human endometrial stromal cells undergo in vitro decidualization when treated with progesterone and estrogen. Using this model, we previously reported specific changes in the c-Src kinase activity and tyrosine phosphorylation of several proteins during in vitro decidualization. Focal adhesion kinase (FAK) and paxillin are known to form a complex with c-Src at the focal contacts and to participate in the integrin-mediated signal transduction as c-Src substrates. We here examined the tyrosine phosphorylation and subcellular localization of the focal adhesion proteins in stromal cells isolated from human endometrium. We found, however, that the total levels of FAK and paxillin tyrosine phosphorylation were not markedly changed during decidualization or after steroid withdrawal. In our culture system, numerous multicellular nodules were developed in cultures of decidualized stromal cells, within whose nodules the focal contacts were found to disappear. Moreover, disruption of the focal contacts was accompanied by disorganization of the actin-based cytoskeleton. These findings suggest that tyrosine phosphorylation of the endometrial paxillin and FAK is not tightly regulated by the kinase activity of c-Src during in vitro decidualization. The escape from regulation by c-Src may be in part due to the dissociation of the focal adhesion proteins/c-Src complex caused by the breakdown of the focal adhesion plaques as well as the loss of the actin-based cytoskeletal architecture.
  • MCP-1受容体を介した情報伝達におけるチロシンキナーゼPyk2の役割の検討
    山崎 雅秀, 荒井 秀典, 石井 賢二, 北 徹, 佐邊 壽孝  動脈硬化  27-  (Suppl.1)  145  -145  1999/11   [Not refereed] [Not invited]
  • 細胞斉一単層形成能とパキシリンの機能
    佐邊 壽孝  日本癌学会総会記事  58回-  39  -39  1999/08   [Not refereed] [Not invited]
  • ARF GAP活性を有するPagはゴルジ構造とパキシリンの細胞内局在制御に関与する
    真崎 雄一, 矢野 元, 大川 克也, 岩松 明彦, 佐邊 壽孝  日本癌学会総会記事  58回-  184  -184  1999/08   [Not refereed] [Not invited]
  • ARF GAP活性を有するパキシリン結合性新規タンパク質
    近藤 明子, 橋本 茂, 真崎 雄一, 佐邊 壽孝  日本癌学会総会記事  58回-  184  -184  1999/08   [Not refereed] [Not invited]
  • 【シグナル伝達の場としての細胞膜ドメイン】 細胞接着形成と細胞内小胞輸送活性
    近藤 明子, 佐邊 壽孝  細胞工学  18-  (8)  1141  -1147  1999/08   [Not refereed] [Not invited]
  • パキシリンを介する細胞運動の接触阻止機構の解析
    中村 邦明, 矢野 元, 佐邊 壽孝  日本癌学会総会記事  58回-  234  -234  1999/08   [Not refereed] [Not invited]
  • パキシリンのチロシンリン酸化を介する細胞-細胞間接触検知機構の解析
    矢野 元, 中村 邦明, 内田 浩, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  58回-  234  -234  1999/08   [Not refereed] [Not invited]
  • 細胞運動におけるパキシリンとp130casの相反的影響
    内田 浩, 明渡 均, 岩崎 輝夫, 佐邊 壽孝  日本癌学会総会記事  58回-  477  -477  1999/08   [Not refereed] [Not invited]
  • ボディープランを司るチロシンリン酸化の意義 細胞運動における細胞間接触感知機構
    佐邊 壽孝  生化学  71-  (8)  656  -656  1999/08   [Not refereed] [Not invited]
  • UCHIDA Hiroshi, YANO Hajime, MAZAKI Yuichi, HASHIMOTO Shigeru, SABE Hisataka  日本分子生物学会年会プログラム・講演要旨集  21-  (0)  1998/12   [Not refereed] [Not invited]
  • YANO Hajime, UCHIDA Hiroshi, SABE Hisataka  日本分子生物学会年会プログラム・講演要旨集  21-  (0)  1998/12   [Not refereed] [Not invited]
  • MAZAKI Yuichi, YANO Hajime, OKAWA Katsuya, HASHIMOTO Shigeru, IWAMATSU Akihiro, SABE Hisatake  日本分子生物学会年会プログラム・講演要旨集  21-  (0)  1998/12   [Not refereed] [Not invited]
  • KONDO Akiko, HASHIMOTO Shigeru, MAZAKI Yuichi, NAGAYAMA Kuniaki, SABE Hisataka  日本分子生物学会年会プログラム・講演要旨集  21-  (0)  1998/12   [Not refereed] [Not invited]
  • HASHIMOTO Shigeru, MAZAKI Yuichi, UCHIDA Hirosi, SABE Hisataka  日本分子生物学会年会プログラム・講演要旨集  21-  (0)  1998/12   [Not refereed] [Not invited]
  • 膜裏打ち分子による細胞内情報伝達 上皮間充織形質転換と細胞生存性・運動性の制御 インテグリン裏打ち蛋白質パキシリン(Paxillin)を中心として
    佐邊 壽孝, 真崎 雄一, 内田 浩, 橋本 茂  生化学  70-  (8)  703  -703  1998/08   [Not refereed] [Not invited]
  • 接着斑タンパク質パキシリン(Paxillin)のゴルジ装置への局在について
    真崎 雄一, 大川 克也, 内田 浩, 橋本 茂, 岩松 明彦, 佐邊 壽孝  日本癌学会総会記事  57回-  146  -146  1998/08   [Not refereed] [Not invited]
  • ヒト癌におけるpaxillin isoformの発現の解析
    内田 浩, 真崎 雄一, 橋本 茂, 佐邊 壽孝  日本癌学会総会記事  57回-  451  -451  1998/08   [Not refereed] [Not invited]
  • 上皮系細胞のインテグリンを介する生存性維持機構に基付いた細胞癌化機構の解析
    橋本 茂, 真崎 雄一, 内田 浩, 佐邊 壽孝  日本癌学会総会記事  57回-  450  -450  1998/08   [Not refereed] [Not invited]
  • Sabe H.  Biophysics  37-  (2)  1997/09   [Not refereed] [Not invited]
  • 【サブメンブレンコート構造と膜蛋白質集積の機構】 インテグリン接着シグナル制御機構の多機能性・多様性創製の基本因子の解明にむけて
    佐邊 壽孝  生物物理  37-  (Suppl.2)  S9  -S9  1997/09   [Not refereed] [Not invited]
  • がん遺伝子とシグナル伝達 細胞接着とシグナル伝達
    佐邊 壽孝  蛋白質・核酸・酵素  42-  (10)  1541  -1550  1997/07   [Not refereed] [Not invited]
  • インテグリンを介した細胞基質間接着とシグナル伝達
    佐邊 壽孝  日本医師会雑誌  118-  (2)  225  -225  1997/07   [Not refereed] [Not invited]
  • 細胞接着とシグナル伝達 インテグリンを介した細胞基質間接着におけるシグナル伝達
    真崎 雄一, 佐邊 壽孝  組織培養工学  23-  (6)  218  -222  1997/05   [Not refereed] [Not invited]
  • 細胞基質間接着シグナリング パキシリンの役割
    佐邊 壽孝  組織培養研究  16-  (1)  20  -20  1997/03   [Not refereed] [Not invited]
  • 細胞基質間接着研究の現状と今後の課題
    佐邊 壽孝  実験医学  14-  (17)  2312  -2316  1996/11   [Not refereed] [Not invited]
  • 細胞基質接着斑蛋白質パキシリンは蛋白質結合性,発現特性が異なる複数のアイソフォームから成る
    佐邊 壽孝  日本癌学会総会記事  55回-  76  -76  1996/09   [Not refereed] [Not invited]
  • v-Src癌化細胞における細胞基質間接着はv-Srcによる細胞内蛋白質チロシンリン酸化に関与する
    佐邊 壽孝  日本癌学会総会記事  54回-  158  -158  1995/09   [Not refereed] [Not invited]
  • 基礎研究はがんを制圧できるか v-Crkによる細胞がん化 細胞基質接着斑タンパク質paxillinとv-Crk,Cskとの相互作用を中心として
    佐邊 壽孝  細胞工学  14-  (5)  506  -512  1995/05   [Not refereed] [Not invited]
  • 蛋白-蛋白相互作用によるシグナルの受け渡し 細胞基質間接着,脱接着による細胞内シグナリング
    佐邊 壽孝  実験医学  13-  (6)  704  -711  1995/04   [Not refereed] [Not invited]
  • Kazuhiko Tsuboi, Kazuhiko Tsuboi, Kazunori Hirayoshi, Kaoru Takeuchi, Hisataka Sabe, Yutaka Shimada, Gakuji Ohshio, Takayoshi Tobe, Masakazu Hatanaka  Biochemical and Biophysical Research Communications  146-  (2)  699  -704  1987/07   [Not refereed] [Not invited]  
    We have examined the level of the c-myc transcript in 6 esophageal, 16 gastric, 19 colorectal and 1 anal cancer tissue samples; these included four lymph nodes and six hepatic metastases obtained surgically. The esophageal cancer tissues were without an increase of the c-myc transcript, some of the gastric cancer samples showed a two to three fold increase and most of the colorectal and the one anal cancer samples showed a two to ten fold increase when compared with a normal mucosal layer. Therefore, the level of the c-myc transcript in human gastrointestinal malignacies shows organ dependency. Local, lymphatic, and hepatic metastases showed little difference in the level of c-myc mRNA from that of the primary tumor. © 1987.
  • Hisataka Sabe, Hisataka Sabe, Hisataka Sabe, Hisataka Sabe, Michinari Hamaguchi, Hidesaburo Hanafusa  Oncogene  14-  (15)  1779  -1788  1997/05   [Not refereed] [Not invited]  
    Protein tyrosine phosphorylation accompanies the integrin-mediated cell to substratum adhesion, and is essential for the progression of G1/S phase of the cell-cycle in normal fibroblasts. To examine how cellular protein tyrosine phosphatase (PTPase) activity is involved in regulating the adhesion-dependent protein tyrosine phosphorylation, we employed fibroblast cells bearing an active form of a protein tyrosine kinase (PTK), v-Src. We found that the v-Src induced tyrosine phosphorylation in certain proteins such as tensin, talin, p120, p80/85 (cortactin) and paxillin was greatly reduced when the cell to substratum adhesion was lost. Re-adhesion of the cells onto fibronectin restored these phosphorylation events, while this was inhibited by the addition of RGD peptide. The kinase activity of the v-Src was unchanged by the loss of cell to substratum adhesion. On the other hand, treatment with a protein tyrosine phosphatase inhibitor vanadate caused much the same increase in the v-Src-mediated cellular tyrosine phosphorylation between cells adhered to the culture environments and cells kept in suspension. These data suggest that PTPase(s) appears to be more critical than the v-Src PTK in determining the cell adhesion-dependent protein tyrosine phosphorylation. Moreover, most of the protein tyrosine phosphorylations that are mediated by the v-Src but still dependent on the cell adhesion were indeed greatly reduced during an anchorage-independent growth of v-Src cells. Thus our data collectively indicate that the v-Src induced high level of tyrosine phosphorylation in certain types of proteins are still under the control of the integrin(s) or the cell adhesion to culture substratum, and most of these adhesion-regulated high levels of tyrosine phosphorylations are not essential for the transformed phenotype.
  • M. Pu, A. A. Akhand, M. Kato, M. Hamaguchi, T. Koike, H. Iwata, H. Sabe, H. Suzuki, I. Nakashima  Oncogene  13-  2615  -2622  1996/12   [Not refereed] [Not invited]  
    The kinase activity of p60(c-src) has been shown to be basically regulated through phosphorylation of Y527. We found that catalytic activity of the immunoprecipitated c-Src kinase from NIH3T3 cells was evaluated several folds by exposure to 0.5-50 μM of sulfhydryl-reactive Hg2+. V(max) of the kinase was increased whereas K(m) was decreased. N-acetylcysteine neutralized this Hg2+ effect, suggesting a critical role of the Hg2+ effect, suggesting a critical role of the Hg2+-mediated sulfhydryl modification of the kinase in the mechanism. Addition of protein tyrosine phosphatase inhibitor Na3VO4 into the reaction mixture did not inhibit the Hg2+-mediated activation. Further study revealed that Hg2+ was capable of activating the v-Src kinase lacking Y527 and the c-Src kinase from mutant cells defective of the Y527-phosphorylating Csk kinase. Cyanogen bromide cleavage maps of radiolabeled Src proteins showed that Hg2+ selectively promoted the autophosphorylation at Y416 and that the previously in vivo radiolabeled phosphorous on Y527 was not deleted during the promotion of Y416 autophosphorylation by Hg2+. Phosphoamino acid analysis demonstrated selective promotion of phosphorylation at tyrosine but not at serine/threonine. Not like bivalent Hg2+, monovalent p-chloromercuribenizenesulfonic acid was incapable of activating c-Src kinase. The results suggest a novel Y416 phosphorylation-linked activation pathway for Src kinases which is initially triggered independent of Y527-mediated or serine/threonine phosphorylation-linked regulation, possibly through sulfhydryl-based protein structural modification for functional alteration.
  • Ryuji Yamaguchi, Ryuji Yamaguchi, Yuichi Mazaki, Kiichi Hirota, Shigeru Hashimoto, Hisataka Sabe, Hisataka Sabe  Oncogene  15-  (15)  1753  -1761  1997/11   [Not refereed] [Not invited]  
    Mitotic cells typically lack well-formed focal adhesions. As an approach to explore the dynamic process regulating the focal adhesion assembly, we examined states of focal adhesion proteins during mitosis of the cell cycle. We found that the amount of paxillin was significantly reduced during mitosis of the cell cycle, whereas other focal adhesion proteins including talin, vinculin and Focal Adhesion Kinase did not. Proteolytic degradation appeared to be involved in the mitotic reduction, but transcriptional and/or translational controls of the mRNA were not essential for this downregulation. Moreover, concurrent with the decreased protein level, phosphorylation status of paxillin altered during mitosis; mitotic paxillin was phosphorylated primarily on serine and dephosphorylated on tyrosine while interphase one was phosphorylated both on serine and tyrosine. We found that mitotic phosphorylation created an electrophoretically slow-migrating population of paxillin which was barely detected in interphase cells. This mitotic specific modification occurred with both α and β isoforms of paxillin. We also examined the fate of paxillin protein by changing its protein amount. We found that majority of paxillin overexpressed was subjected to the specific modification but not to the downregulation in the mitotic arrested cells. On the other hand, paxillin exogenously expressed at a moderate level was subjected to both the mitotic modification and downregulation. Collectively, we concluded that paxillin's specific serine phosphorylation together with the proteolytic downregulation of a limited fraction of paxillin is taken place during the mitosis of the cell cycle.
  • Yuichi Mazaki, Yuichi Mazaki, Hiroshi Uchida, Hiroshi Uchida, Hiroshi Uchida, Okio Hino, Shigeru Hashimoto, Shigeru Hashimoto, Hisataka Sabe, Hisataka Sabe, Hisataka Sabe  Journal of Biological Chemistry  273-  (35)  22435  -22441  1998/08   [Not refereed] [Not invited]  
    Paxillin, a focal adhesion protein, exists as multiple isoforms in humans (α, β, and γ). To understand more about the physiological role of each isoform, we have employed the mouse system. We found that although the α and β isoforms are present in the mouse, the γ isoform is not. The α isoform protein was detected clearly in most adult tissues, whereas the β isoform protein was almost undetectable except in spleen, testis, thymus, and lung. On the other hand, mRNAs of both isoforms were detectable in all tissues we examined. High levels of the β isoform protein was detected in peritoneal exudate macrophage cells in adult mouse as well as in cultured fibroblasts, together with the α isoform. The α isoform was expressed at a constant level throughout the embryonic stages we examined, whereas the β isoform protein was detected at the mid-stages of development and increased to levels almost equal to those of the α isoform during the late stages of embryogenesis. Therefore, unlike the α isoform, expression of the β isoform protein is restricted in adult tissues. Moreover, we showed that α and β isoforms were colocalized within the same focal adhesion plaques, and cytoplasmic pools of both isoforms exist in the perinuclear area, colocalized with the Golgi apparatus.
  • Naoyuki Nishiya, Hisataka Sabe, Kiyoshi Nose, Motoko Shibanuma  Nucleic Acids Research  26-  (18)  4267  -4273  1998/09   [Not refereed] [Not invited]  
    hic-5 protein is a member of the LIM protein family, containing four LIM domains in its C-terminal region. It is mainly localized in focal adhesions and shows striking similarity to paxillin in its LIM domains, although the function of these LIM domains has remained elusive. In the present study, we found that full-length and the C-terminal half of hic-5 protein, including four LIM domains, bound to DNA in a zinc-dependent manner in vitro. Mouse genomic fragments that specifically bound to the hic-5 protein were isolated by successive rounds of hic-5 protein-DNA complex immunoprecipitation and PCR amplification. Seven independent clones were isolated, which contained high amounts of G+A and/or a long A/T tract. A DNA binding protein blot assay revealed the specificity of the interaction between hic-5 protein and the DNA fragment. Using a series of truncated forms of the hic-5 LIM domains, each of the four LIM domains was found to contribute to DNA binding in a distinctive manner.
  • Takashi Hiiragi, Hiroyuki Sasaki, Hiroyuki Sasaki, Akira Nagafuchi, Hisataka Sabe, Shen Chun Shen, Masato Matsuki, Kiyofumi Yamanishi, Shoichiro Tsukita, Shoichiro Tsukita  Journal of Biological Chemistry  274-  (48)  34148  -34154  1999/11   [Not refereed] [Not invited]  
    Transglutaminase type I was identified as a tyrosine-phosphorylated protein from the isolated junctional fraction of the mouse liver. This enzyme was reported to be involved in the covalent cross-linking of proteins in keratinocytes, but its expression and activity in other cell types have not been examined. Northern blotting revealed that transglutaminase type 1 was expressed in large amounts in epithelial tissues (lung, liver, and kidney), which was also confirmed by immunoblotting with antibodies raised against mouse recombinant protein. Immunoblotting of the isolated junctional fraction revealed that transglutaminase type 1 was concentrated in the fraction not only as a 97-kDa form but also as forms of various molecular masses cross- linked to other proteins. In agreement with this finding, endogenous transglutaminase type 1 was immunofluorescently colocalized with E-cadherin in cultured simple epithelial cells. In the liver and kidney, immunoelectron microscopy revealed that transglutaminase type 1 was concentrated, albeit not exclusively, at cadherin-based adherens junctions. Furthermore, by in vitro and in vivo labeling, transglutaminase cross-linking activity was also shown to be concentrated at intercellular junctions of simple epithelial cells. These findings suggested that the formation of covalently cross-linked multimolecular complexes by transglutaminase type I is an important mechanism for maintenance of the structural integrity of simple epithelial cells, especially at cadherin-based adherens junctions.
  • Takayuki Kanazawa, Sachiko Nakamura, Michiko Momoi, Toshiyuki Yamaji, Hiromu Takematsu, Hajime Yano, Hisataka Sabe, Akitsugu Yamamoto, Toshisuke Kawasaki, Yasunori Kozutsumi, Yasunori Kozutsumi  Journal of Cell Biology  149-  (4)  943  -950  2000/05   [Not refereed] [Not invited]  
    Although a number of cellular components of cytokinesis have been identified, little is known about the detailed mechanisms underlying this process. Here, we report that the lipid metabolite psychosine (galactosylsphingosine), derived from galactosylceramide, induced formation of multinuclear cells from a variety of nonadherent and adherent cells due to inhibition of cytokinesis. When psychosine was added to the human myelomonocyte cell line U937, which was the most sensitive among the cell lines tested, cleavage furrow formed either incompletely or almost completely. However, abnormal contractile movement was detected in which the cellular contents of one of the hemispheres of the contracting cell were transferred into its counterpart. Finally, the cleavage furrow disappeared and cytokinesis was reversed. Psychosine treatment also induced giant clots of actin filaments in the cells that probably consisted of small vacuoles with filamentous structures, suggesting that psychosine affected actin reorganization. These observations could account for the formation of multinuclear globoid cells in the brains of patients with globoid cell leukodystrophy, a neurological disorder characterized by the accumulation of psychosine due to galactosylceramidase deficiency.
  • Hajime Yano, Hiroshi Uchida, Teruo Iwasaki, Mutsuko Mukai, Hitoshi Akedo, Hitoshi Akedo, Kuniaki Nakamura, Shigeru Hashimoto, Hisataka Sabe, Hisataka Sabe  Proceedings of the National Academy of Sciences of the United States of America  97-  (16)  9076  -9081  2000/08   [Not refereed] [Not invited]  
    Protein tyrosine phosphorylation accompanies and is essential for integrin signaling. We have shown that tyrosine phosphorylation of paxillin α and Crk-associated substrate (p130(Cas)) is a prominent event on integrin activation in normal murine mammary gland epithelial cells. Tyrosine phosphorylation of p130(Cas) has been demonstrated to facilitate cell migration. We show here that tyrosine phosphorylation of paxillin α acts to reduce haptotactic cell migrations as well as transcellular invasive activities in several different experimental cell systems, whereas tyrosine phosphorylation of p130(Cas) exerts opposing effects to those of paxillin α. Each of the phosphorylation-null mutants acts as a dominant negative for each phenotype. Moreover, we found that overexpression of paxillin α reduced the cell saturation density of normal murine mammary gland cells, whereas overexpression of p130(Cas) increased it. These effects also seemed to depend on tyrosine phosphorylation events. Cell growth rates and morphologies at growing phases were not significantly altered, nor were cells transformed. Addition of epidermal growth factor increased saturation density of the paxillin α-overexpressing cells, whereas no further increment was observed in p130(Cas)-overexpressing cells. We propose that tyrosine phosphorylation of paxillin α and p130(Cas) exerts opposing effects on several integrin-mediated cellular events, possibly through different signaling pathways.
  • Akiko Suzuki, Nae Kadota, Tomokazu Hara, Yoshiko Nakagami, Toshiaki Izumi, Tadaomi Takenawa, Hisataka Sabe, Takeshi Endo  Oncogene  19-  (51)  5842  -5850  2000/11   [Not refereed] [Not invited]  
    Meltrin α/ADAM12 is a member of the ADAM/MDC family proteins characterized by the presence of metalloprotease and disintegrin domains. This protein also contains a single transmembrane domain and a relatively long cytoplasmic domain containing several proline-rich sequences. These sequences are compatible with the consensus sequences for binding the Src homology 3 (SH3) domains. To determine whether the proline-rich sequences interact with SH3 domains in several proteins, binding of recombinant SH3 domains to the meltrin α cytoplasmic domain was analysed by pulldown assays. The SH3 domains of Src and Yes bound strongly, but that of Abl or phosphatidylinositol 3-kinase p85 subunit did not. Full-length Grb2/Ash bound strongly, whereas its N-terminal SH3 domain alone did less strongly. Src and Grb2 in bovine brain extracts also bound to meltrin α cytoplasmic domain on affinity resin. Furthermore, immunoprecipitation with a monoclonal antibody to meltrin α resulted in coprecipitation of Src and Grb2 with meltrin α in cell extracts, suggesting that Src and Grb2 are associated in vivo with meltrin α cytoplasmic domain. This notion was also supported by the findings that exogenously expressed meltrin α cytoplasmic domain coexisted with Src and Grb2 on the membrane ruffles. The C-terminal Tyr901 of meltrin α was phosphorylated both in vitro and in cultured cells by v-Src. These results may imply that meltrin α 8cytoplasmic domain is involved in a signal transduction for some biological function through the interaction with SH3-containing proteins.
  • Shigeru Hashimoto, Asako Tsubouchi, Asako Tsubouchi, Yuichi Mazaki, Hisataka Sabe, Hisataka Sabe, Hisataka Sabe  Journal of Biological Chemistry  276-  (8)  6037  -6045  2001/02   [Not refereed] [Not invited]  
    p21-activated kinases (PAKs) are implicated in integrin signalings, and have been proposed to associate with paxillin indirectly. We show here that paxillin can bind directly to PAK3. We examined several representative focal adhesion proteins, and found that paxillin is the sole protein that associates with PAK3. PAK3 associated with the α and β isoforms of paxillin, but not with γ. We also show that paxillin α associated with both the kinase-inactive and the Cdc42-activated forms of PAK3 in vivo, without affecting the activation states of the kinase. A number of different functions have been ascribed to PAKs; and PAKs can bind directly to growth factor signaling-adaptor molecule, Nck, anda and a guanine nucleotide exchanger, βPIX. Our results revealed that paxillin α can compete with Nck and βPIX in the binding of PAK3. Moreover, paxillin α can be phosphorylated by PAK3 at serine. Therefore, paxillin α but not γ, appears to be capable of linking both the kinase-inactive and activated forms of PAK3 to integrins independent of Nck and βPIX, as Nck links PAK1 to growth factor receptors. Our results also revealed that paxillin is involved in highly complexed protein-protein interactions in integrin signaling.
  • Kuniaki Nakamura, Hajime Yano, Erik Schaefer, Hisataka Sabe, Hisataka Sabe  Oncogene  20-  (21)  2626  -2635  2001/05   [Not refereed] [Not invited]  
    Integrin signaling is activated during epithelial-mesenchymal transdifferentiation (EMT) and cell migration, processes serving as models for carcinogenesis. We have shown that paxillin and p130Cas become highly tyrosine phosphorylated during these processes in NMuMG cells. Here, we examined the regulation of Fak and Pyk2, kinases implicated in this phosphorylation. Pyk2 became phosphorylated at the major autophosphorylation site (Tyr-402) and the potential Grb2-binding site (Tyr-881) during EMT. In contrast, phosphorylation of Fak at the corresponding autophosphorylation site (Tyr-397) occurred even in sedentary epithelial cells, whereas phosphorylation at Tyr-407 and Tyr-861 was induced during EMT. During cell migration, these phosphorylation events, except Fak Tyr-397, were augmented further, and phosphorylation of Fak Tyr-577 and the corresponding Pyk2 Tyr-580, both within the kinase activation loops, was also induced. In all cases, phosphorylation of the putative Grb2-binding site in Fak (Tyr-925) was almost undetectable. Although Fak and Pyk2 have several phosphorylation sites in common, Tyr-407 and Tyr-861 are unique to Fak. Our results revealed that Fak and Pyk2 are non-equivalent in the tyrosine phosphorylation events and thereby likely to evoke different downstream signaling cascades during EMT and cell migration of NMuMG cells. We also show that Fak Tyr-397 phosphorylation occurs exclusively at the cytoplasm, but not at focal contacts, in the sedentary epithelial cells. In contrast, all other tyrosine phosphorylated forms of Fak and Pyk2 are predominantly localized to focal adhesions and the cell periphery in motile cells, all colocalized with paxillin and p130Cas.
  • FEBS Letters  133-  (2)  311  -315  1981   [Not refereed] [Not invited]
  • Gene  31-  (1/3)  279  -283  1984   [Not refereed] [Not invited]
  • J.Gen.Appl.Microbiol  30-  27  -33  1984   [Not refereed] [Not invited]
  • Primary structure of phosphoenolpyruvate carboxylase in E.coli.(共著)
    Proceedings of the 34th Meeting on Protein Structure  105  -108  1983   [Not refereed] [Not invited]
  • Nucleic Acids Res.  13-  (1)  59  -71  1985   [Not refereed] [Not invited]
  • Nature  311-  (5987)  631  -635  1984   [Not refereed] [Not invited]
  • Genomic structure of HTLV (human T cell Leukemia virus) : detection of defective genome and its amplication in MT-2 cells.(共著)
    EMBO J.  3-  1339  -1343  1984   [Not refereed] [Not invited]
  • Nucleic Acids Res.  13-  (5)  1505  -1516  1985   [Not refereed] [Not invited]
  • Nucleic Acids Res.  13-  7579  -7589  1985   [Not refereed] [Not invited]
  • Structure analysis of p28 adult T cell leukemia-associated antigen.(共著)
    J.Gen.Virol.  67-  1373  -1379  1986   [Not refereed] [Not invited]
  • Expression of a provirus of human T cell leukemia virus type (]G0001[) by DNA transfection.(共著)
    J.Gen.Virol.  68-  499  -506  1987   [Not refereed] [Not invited]
  • Establishment of an IL2 dependent T cell Line from a patient with a multiple seclerosis, which express unregulated IL2 receptor and has clonal abnormality 21 trisomy.(共著)
    Int.J.Immunolotherapy  8-  (3)  123  -131  1991   [Not refereed] [Not invited]
  • Nature  327-  (6117)  64  -67  1987   [Not refereed] [Not invited]
  • Differential effects on interleukin 2 receptors (p75 and p55) by the pXgene of HTLV-(]G0001[) virus.(共著)
    Inter.J.Cancer  41-  880  -885  1988   [Not refereed] [Not invited]
  • Molecular analysis of the formation of the high affinity interlsukin 2 receptor.(共著)
    Mol.Biol.Med.  5-  123  -138  1988   [Not refereed] [Not invited]
  • HTLV-1 p27rex stabilaizes human interleukin 2 receptor a chain m RNA.(共著)
    EMBO J.  9-  4164  -4166  1990   [Not refereed] [Not invited]
  • Effecient transient expression of cDNA in CTLL-2 cells expressing polyoma large-antigen.(共著)
    Technique  2-  189  -193  1990   [Not refereed] [Not invited]
  • Stepwise formation of the high-affinity complex of the interleukin 2 receptor.(共著)
    Inter.Immunol.  2-  1165  -1177  1990   [Not refereed] [Not invited]
  • Inter.Immunol.  3-  (11)  1137  -1148  1991   [Not refereed] [Not invited]
  • Biochemical evidence for a third chain of the interleukin-2 receptor.(共著)
    J.Biol.Chem.  266-  22186  -22191  1991   [Not refereed] [Not invited]
  • Proc.Natl.Acad.Sci.USA  89-  (6)  2190  -2194  1992   [Not refereed] [Not invited]
  • IL-2 can support growth of CD8+ T cells but not CD4+ T cells of human IL-2 receptor β-chain transgenic mice.(共著)
    J.Immunol.  153-  5373  -5381  1994   [Not refereed] [Not invited]
  • Comparative study of three protein tyrosine phosphatases : ChPTP1 specifically dephosphorylates c-Src tyrosine 527.(共著)
    J.Biol.Chem.  269-  20194  -20200  1994   [Not refereed] [Not invited]
  • Tyrosine kinase Lyn and Syk regulate B cell receptor-coupled calcium mobilization through distinct pathways.(共著)
    EMBO J.  13-  1341  -1349  1994   [Not refereed] [Not invited]
  • Specific motifs recognized by the SH2 domains of Csk, 3BP2, fes/fps,Grb-2, SHPTP1, SHC, Syk and Vav.(共著)
    Mol.Cell.Biol.  14-  2777  -2785  1994   [Not refereed] [Not invited]
  • Functional analysis of Csk in signal transduction through the B cell antigen receptor.(共著)
    Mol.Cell.Biol.  14-  7306  -7313  1994   [Not refereed] [Not invited]
  • J.Biol.Chem.  270-  (52)  31219  -31224  1995   [Not refereed] [Not invited]
  • CSK Enhances Insulin-stimulated Dephosphorylation of focal adhesion proteins.(共著)
    Mol.Cell.Biol.  16-  4765  -4772  1996   [Not refereed] [Not invited]
  • J.Biol.Chem.  271-  (48)  30487  -30492  1996   [Not refereed] [Not invited]
  • Genomic expression of human T-lymphotropic virus (HTLV-(]G0001[)).(共著)
    AIDS Res.  2-  s79-s85  1986   [Not refereed] [Not invited]
  • Structure and function of the interleukin 2 receptor : affinity conversion model.(共著)
    Immunological Rev.  92-  103  -120  1986   [Not refereed] [Not invited]
  • Molecular genetic studies on the interleukin 2 receptor.(共著)
    Recent Advance in Leukemia and Lymphoma  309  -312  1987   [Not refereed] [Not invited]
  • The Jouanal of Biological Chemistry  272-  (11)  7437  -7444  1997   [Not refereed] [Not invited]
  • FEBS lett.  399-  (1/2)  53  -58  1996   [Not refereed] [Not invited]
  • Endocrinology  140-  2632  -2636  1999   [Not refereed] [Not invited]
  • Vascular endothelial growth factor(VEGF) induces activation and subcellular trnaslocation of focal adhesion kinase(pp125FAK) in cultured rat cardiac myocytes.
    Circ. Res.  84-  1194  -1202  1999   [Not refereed] [Not invited]
  • Biophy. Biochem. Res. Com.  262-  (1)  290  -296  1999   [Not refereed] [Not invited]
  • Tyrosine phosphorylation and subcelluar localization of focal adhesion proteins during in vitro decidualization of human endometrial stromal cells.
    Endocrinology.  140-  5982  -5990  1999   [Not refereed] [Not invited]
  • Biopby, Biochem.Res.Com  262-  (1)  290  -296  1999   [Not refereed] [Not invited]
  • EMBO J.  19-  (4)  562  -571  2000   [Not refereed] [Not invited]
  • A new paxillin-binding protein, PAG3/Papd/KIAA 0400, bearing an Arf GTPase-activating protein activity is involved in paxillin recruitment to focal adhesions and cell migration.
    Mol. Biol. Cell  11-  1315  -1327  2000   [Not refereed] [Not invited]
  • A new paxillin-binding protein, PAG3/Pap αKIAA0400, bearing an ARF GTPase-activating protein activity, is involved in paxillin recruitment to focal adhesions and cell migration.(共著)
    Mol.Biol.Cell  11-  1315  -1327  2000   [Not refereed] [Not invited]
  • An ADP-Ribosylation Factor GTPase-activating Protein Git2-short/KIAA0148 Is Involved in Subcellular Localization of Paxillin and Actin Cyeoskeletal Organization.(共著)
    Mol.Biol.Cell  12-  645  -662  2001   [Not refereed] [Not invited]
  • EMBO report  2-  (814-820)  2001   [Not refereed] [Not invited]
  • Paxillin-associated ArfGAPs-their isoform specificities and roles in coordination-in
    The ARF Book   [Not refereed] [Not invited]
  • J. Biochem. Minireview(in press)   [Not refereed] [Not invited]
  • Mol. Cell Biol.  23-  (15)  5331  -5345  2003   [Not refereed] [Not invited]  
    C. Didier, L. Broday, A. Bhoumik, S. Israeli, S. Takahashi, K. Nakayama, S. M. Thomas, C. E. Turner, S. Henderson, H. Sabe. & Z. Ronai. RNF5 - a RING finger protein that regulates cell motility by targeting paxillin ubiquitination and altered localization.
  • A. J. Woods, M. S. Roberts, J. Choudhary, S. T. Barry, Y. Mazaki, H. Sabe, S. J. Morley, D. R. Critchley & J. C. Norman. Paxillin associates with poly(A)-binding protein lat the dense ER and the leading edge of migrating cells
    J. Biol. Chem.  227-  6428  -6437  2002   [Not refereed] [Not invited]
  • Ensemble of membrane and cytoskeleton remodelings in cell migration
    Seikagaku  74(12):1429-40-  2002   [Not refereed] [Not invited]
  • Watanabe H, Shimizu T, Nishihira J, Abe R, Nakayama T, Taniguchi M, Sabe H, Ishibashi T, Shimizu H. Ultraviolet A-induced production of matrix metalloproteinase-1 is mediated by macrophage migration inhibitory factor (MIF) in human dermal fibroblasts.
    J Biol Chem.  279(3):1676-83-  2003   [Not refereed] [Not invited]
  • J Biochem.  134(4):485-9-  2003   [Not refereed] [Not invited]
  • Hashimoto S, Onodera Y, Hashimoto A, Tanaka M, Hamaguchi M, Yamada A, Sabe H. Requirement for Arf6 in breast cancer invasive activities.
    Proc Natl Acad Sci U S A.  101(17):6647-52.-  2004   [Not refereed] [Not invited]
  • Romanova LY, Hashimoto S, Chay KO, Blagosklonny MV, Sabe H, Mushinski JF. Phosphorylation of paxillin tyrosines 31 and 118 controls polarization and motility of lymphoid cells and is PMA-sensitive.
    J Cell Sci.  117(Pt 17):3759-68.-  2004   [Not refereed] [Not invited]
  • Yano H, Mazaki Y, Kurokawa K, Hanks SK, Matsuda M, Sabe H. Roles played by a subset of integrin signaling molecules in cadherin-based cell-cell adhesion.
    J Cell Biol.  166(2):283-95.-  2004   [Not refereed] [Not invited]
  • Kojima C, Hashimoto A, Yabuta I, Hirose M, Hashimoto S, Kanaho Y, Sumimoto H, Ikegami T, Sabe H. Regulation of Bin1 SH3 domain binding by phosphoinositides.
    EMBO J.  2004   [Not refereed] [Not invited]
  • EMBO J.  24:963-973.-  2005   [Not refereed] [Not invited]  
    Y. Onodera, S. Hashimoto, A. Hashimoto, M. Morishige, Y. Mazaki, A. Yamada, E. Ogawa, M. Adachi, T. Sakurai, T. Manabe, H. Wada, N. Matsuura & H. Sabe. Expression of AMAP1, an ArfGAP, provides novel targets to inhibit breast cancer invasive activities. 2005.
  • AJ. Woods, T. Kantidakis, H. Sabe, DR. Critchley & JC. Norman. Interaction of paxillin with poly(A)-binding protein 1 and its role in focal adhesion turnover and cell migration.
    Mol.Cell Biol.  25:3763-3773.-  2005   [Not refereed] [Not invited]  
    2005.

Research Grants & Projects

  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(A))
    Date (from‐to) : 2008 -2011 
    Author : Hisataka SABE
     
    (財)大阪バイオサイエンス研究所->北海道大学(抄録なし)
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(特定領域研究)
    Date (from‐to) : 2005 -2009 
    Author : Hisataka SABE
     
    (財)大阪バイオサイエンス研究所->北海道大学Most malignant human tumors are epithelial cell origin. The basic fear of such tumors are based on their invasion and metastasis. Activation of integrins and inactivation of E-cadherin are hallmark characteristics for such invasive and metastatic properties. Here our purpose is to understanding the underlying molecular mechanisms for integrin activation and E-cadherin inactivation in the malignant development of tumor cells.
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2006 -2007 
    Author : Hisataka SABE
     
    (財)大阪バイオサイエンス研究所We aim to elucidate mechanisms controlling cell migration and the polarity formation, via investigating their relationship to intracellular vesicle trafficking. Our other main research interest is to understand the principal mechanisms involved in maintenance of epithelial tissue integrity, as well as cancer cell invasion and metastasis which occurs as a result of the disruption of the epithelial integrity. Although biology is a diverse subject, we are constantly aiming towards understanding whether a common fundamental mechanism actually exists behind the complicated phenomena of living or...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2004 -2005 
    Author : Hisataka SABE
     
    (財)大阪バイオサイエンス研究所Cell migration is a multifactorial process in which a number of distinct events occur simultaneously. The major purpose of this study is to understand basic molecules and mechanisms coordinately regulating cell migration and invasion.Arf6 plays essential roles in recycling of plasma membrane component, as well as both membrane and cytoskeletal remodeling at cell peripheries. We have previously identified several proteins bearing ArfGAP domains as binding proteins to paxillin, an integrin signaling adaptor/scaffolding protein. These ArfGAPs include AMAP1 and AMAP2. We have also shown that AM...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2002 -2003 
    Author : Hisataka SABE
     
    (財)大阪バイオサイエンス研究所Previously we reported that AMAP2/PAG3/Papα/KIAAO400, a GTPase-activating protein (GAP), acts to antagonize Arf6 function when overexpressed, while it was shown to exhibit efficient GAPing activities for other Arf isoforms in vitro. During this period of the two fiscal years we first found that AMAP2, through its ArfGAP domain, binds to GTP-Arf6, but not to GDP-Arf6 nor other Arfs irrespective of nucleotide status. The majority of AMAP2 was localized to intracellular tubulovesicular structures, and redistributed to Arf6-enriched membrane areas upon Arf6 activation. In HeLa cells, Arf6 has b...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2000 -2001 
    Author : Hisataka SABE
     
    (財)大阪バイオサイエンス研究所ARF6 regulates endosomal recycling. We have shown that PAG3/Papα/KIAA0400 acts as a GTPase-activation protein (GAP) specific for ARF6.We study here molecular mechanims how PAG3 is involved in endosomal recycling to be an ARF6GAP. We found that PAG3, via its proline-rich region, binds to the src homology 3 (SH3) domain of several components of the endocytic machinery, and analysed its interaction with amphiphysin IIa. PAG3 existed at ARF6(Q67L)-positive membrane ruffles colocalized with amphyphysin Ha, but the majority exists at intracellular tubulovesicular structure. Overexpression of the ...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 1998 -2001 
    Author : Hisataka SABE
     
    京都大学->(財)大阪バイオサイエンス研究所Temporal and spatial regulation of actin-based cytoskeletal organization and focal adhesion formation play an essential role in cell migration. We found that tyrosine phosphorylation of paxillin and pi3OCas was a prominent event upon integrin activation during epithelial-mesenchymal transdifferentiation and cell migration. Tyrosine phosphorylation of p130^ has been demonstrated to facilitate cell migration. We showed that tyrosine phosphorylation of paxillin cc acts to reduce haptotactic cell migration as well as transcellular invasive activities in several different experimental cell ...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(総合研究(A), 基盤研究(A))
    Date (from‐to) : 1995 -1996 
    Author : Kiyotoshi SEKIGUCHI
     
    大阪府立母子保健総合医療センター研究所->大阪府立母子保健総合医療センター・研究所->大阪府立母子保健総合医療センター研究所->大阪府立母子保健総合医療センター・研究所(1) Alternative splicing of the fibronectin pre-nRNA at the EDA region was found to regulate the cell-adhesive and integrin alpha5beta1 binding activities of fibronectin. This is the first evidence for the regulation of the integrin-mediated signal transduction by alternative splicing of the extracellular matrix components. (2) The integrin alpha3beta1 binding on laminin-5 was localized in the G2 domain using a series of bacterially produced recombinant fragments derived from different domains of laminin-5. (3) Novel isoforms of paxillin, a crucial adaptor molecule associated with integrins...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(国際学術研究)
    Date (from‐to) : 1995 -1996 
    Author : 淀井 淳司, Junji YODOI
     
    京都大学Human thioredoxin (TRX) has a potent thiol reducing activity and plays an important role on the redox regulation. Yodoi and the the members of the international cooperation program of the redox regulation and cellular signal transduction demonstrated the following results : 1) the targeted disruption of the TRX was embryonic lethal, suggesting the essential role of TRX in the mouse embryogenesis and differentiation. 2) the oxidative responsive element in the thioredoxin promoter was identified. 3) TRX and Ref-1 which is important for the activation of the AP-1 was demonstrated to be able to...
  • Molecular Mechanism and Signaling of Cell to Substratum Adhesion

Educational Activities

Teaching Experience

  • 研究発表技法Ⅰ
    開講年度 : 2017
    課程区分 : 修士課程
    開講学部 : 医学院
  • Master's Thesis Research in Medical Sciences
    開講年度 : 2017
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : シグナル伝達、EMT、細胞内トラフィック、癌、浸潤転移、モデルマウス
  • 研究発表技法Ⅱ
    開講年度 : 2017
    課程区分 : 修士課程
    開講学部 : 医学院
  • Basic Principles of Medicine
    開講年度 : 2017
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : シグナル伝達、EMT、細胞内トラフィック、癌、浸潤転移、モデルマウス
  • 研究発表技法Ⅰ
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Principles of Medicine
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : シグナル伝達、EMT、細胞内トラフィック、癌、浸潤転移、モデルマウス
  • 研究発表技法Ⅱ
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Dissertation Research in Medical Sciences
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : シグナル伝達、EMT、細胞内トラフィック、癌、浸潤転移、モデルマウス
  • 基盤医学研究Ⅰ
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • BiochemistryⅡ
    開講年度 : 2017
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 分子生物学、細胞生物学
  • 基盤医学研究Ⅱ
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • 医学総論
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • 研究発表技法Ⅰ
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • 研究発表技法Ⅱ
    開講年度 : 2017
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • 選択実習Ⅰ
    開講年度 : 2017
    課程区分 : 学士課程
    開講学部 : 医学部
  • 選択実習Ⅱ
    開講年度 : 2017
    課程区分 : 学士課程
    開講学部 : 医学部


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