Regulation of ErbB signaling by N-glycan

• Project/Area Number: 21590342
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Sapporo Medical University
• Principal Investigator: TAKAHASHI Motoko 札幌医科大学, 医学部, 准教授 (00303941)
• Co-Investigator(Renkei-kenkyūsha): NISHITANI Chiaki 札幌医科大学, 医学部, 助教 (30381255)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 増殖因子受容体 / ErbB / N型糖鎖 / 糖鎖生物学 / 蛋白質化学 / 生化学

Research Abstract

The aim of this study is to understand the mechanisms by which N-glycan regulate function and structure of ErbB. We prepared the extracellular domain of ErbB(sErbB) and N418Q mutant of ErbB3. sErbB3 suppressed heregulin signaling more effectively than ErbB2 or ErbB4, and N418Q mutant suppressed more than wild type. Cell proliferation-inhibitory activity of sErbB3 was also upregulated by N418Q mutation. The results indicate that N-glycan on Asn418 of ErbB3 regulates the ErbB3 signaling.

Research Products

• [Journal Article] Pulmonary surfactant protein A protects lung epithelium from cytotoxicity of humanβ-defensin 3 (2012)
  • Author(s): Saito A., Ariki S., Sohma H., Nishitani C., Inoue K., Ebata N., Takahashi M., Hasegawa Y., Kuronuma K., Takahashi H., Kuroki Y.
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 15034-15043
  • Peer Reviewed
• [Journal Article] Measurement of peroxiredoxin-4 in rat tissues and implication of its serum level as a potential marker for hepatic disease (2012)
  • Author(s): Ito R., Takahashi M., Ihara H., Tsukamoto H., Fujii J., Ikeda Y.
  • Journal Title: Int. J. Mol. Med. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Development of an enzyme-linked immunosorbent assay for the measure ment of Prx-4 in rat tissues : a potential marker for hepatic oxidative stress (2012)
  • Author(s): Ito R., Takahashi M., et al
  • Journal Title: Int.J.Mol.Med. Volume: 29(in press)
  • Peer Reviewed
• [Journal Article] Pulmonary surfactant protein A protects lung epithelium from cytotoxicity of human β-defensin 3 (2012)
  • Author(s): Saito A., et al
  • Journal Title: J.Biol.Chem Volume: 287(in press)
  • Peer Reviewed
• [Journal Article] Pulmonary collectins play distinct roles in host defense against Mycobacterium Avium (2011)
  • Author(s): Ariki S., Kojima T., Gasa S., Saito A., Nishitani C., Takahashi M., Shimizu T., Kurimura Y., Sawada N., Fujii N., Kuroki Y.
  • Journal Title: J. Immunol. Volume: 187 Pages: 2586-2594
  • Peer Reviewed
• [Journal Article] Pulmonary collectins play distinct roles in host defense against Mycobac terium Avium (2011)
  • Author(s): Arki S., et al
  • Journal Title: J.Immnol. Volume: 187 Pages: 2586-2594
  • Peer Reviewed
• [Journal Article] Spontaneous skin damage and delayed wound healing in SOD1-deficient mice (2010)
  • Author(s): Iuchi Y., Roy D., Okada F., Kibe N., Tsunoda S., Suzuki S., Takahashi M., Yokoyama H., Yoshitake J., Kondo S., Fujii J.
  • Journal Title: Mol. Cell. Biochemistry Volume: 341 Pages: 181-194
  • Peer Reviewed
• [Journal Article] Pulmonary collectins protect macrophages against pore-forming activity of Legionella pneumophila and suppress its intracellular growth (2010)
  • Author(s): Sawada K., Ariki S. Kojima T., Saito A., Yamazoe M., Nishitani C., Shimizu T., Takahashi M., Mitsuzawa H., Yokota S., Sawada N., Fujii N., Takahashi H., Kuroki Y.
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 8434-8443
  • Peer Reviewed
• [Journal Article] Spontaneous skin damage and delayed wound healing in SOD1-deficienct mice. (2010)
  • Author(s): Iuchi Y., et al.
  • Journal Title: Mol.Cell.Biochem. Volume: 341 Pages: 181-194
  • Peer Reviewed
• [Journal Article] Pulmonary collectins protect macrophages against pore-forming activity of Legionella pneumophila and suppress its intracellular growth. (2010)
  • Author(s): Sawada K., et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 8434-8443
  • Peer Reviewed
• [Journal Article] Pulmonary collectins protect macrophages against pore-forming activity of Legionella pneumophila and suppress its intracellular growth. (2010)
  • Author(s): Sawada K., et al.
  • Journal Title: J.Biol.Chem. 285 Pages: 8434-8443
  • Peer Reviewed
• [Journal Article] Spontaneous skin damage and delayed wound healing in SOD1-deficient mice. (2010)
  • Author(s): Iuchi Y., et al.
  • Journal Title: Mol.Cell.Biochem. (in press)
  • Peer Reviewed
• [Journal Article] Core fucosylation of E-cadherin enhances cell-cell adhesion in human colon carcinoma WiDr cells (2009)
  • Author(s): Osumi D., Takahashi M., Miyoshi E., Yokoe S., Lee SH., Noda K., Nakamori S., Gu J., Ikeda Y., Kuroki Y., Sengoku K., Ishikawa M., Taniguchi N.
  • Journal Title: Cancer Sci. Volume: 100 Pages: 888-895
  • NAID: 10025145697
  • Peer Reviewed
• [Journal Article] Mutational analysis of Cys88 of Toll-like receptor 4 highlights the critical role of MD-2 in cell surface receptor expression (2009)
  • Author(s): Nishitani C., Takahashi M., Mitsuzawa H., Shimizu T., Ariki S., Matsushima N., Kuroki Y.
  • Journal Title: Int Immunol. Volume: 21 Pages: 925-934
  • Peer Reviewed
• [Journal Article] Mannose binding lectin and lung collectins interact with Toll-like receptor 4 and MD-2 by different mechanisms (2009)
  • Author(s): Shimizu T., Nishitani C., Mitsuzawa H., Ariki S., Takahashi M., Ohtani K., Wakamiya N., Kuroki Y.
  • Journal Title: Biochim. Biophys Acta-General Subjects Volume: 1790 Pages: 1705-1710
  • Peer Reviewed
• [Journal Article] Core fucose and bisecting GlcNAc, the direct modifiers of N-glycan core ; Their functions and target proteins (2009)
  • Author(s): Takahashi M., Kuroki Y., Ohtsubo K., and Taniguchi N.
  • Journal Title: Carbohydrate Res. Volume: 344 Pages: 1387-1390
  • Peer Reviewed
• [Journal Article] Core fucosylation of E-cadherin enhances cell-cell adhesion in human colon carcinoma WiDr cells. (2009)
  • Author(s): Osumi D., Takahashi M., et al.
  • Journal Title: Cancer Sci. 100 Pages: 888-895
  • NAID: 10025145697
  • Peer Reviewed
• [Journal Article] Core fucose and bisecting GIcNAc, the direct modifiers of N-glycan core ; Their functions and target proteins. (2009)
  • Author(s): Takahashi M., et al.
  • Journal Title: Carbohyd.Res. 344 Pages: 1387-1390
  • Peer Reviewed
• [Journal Article] Mutational analysis of Cys88 of Toll-like receptor 4 highlights the critical role of MD-2 in cell surface receptor expression. (2009)
  • Author(s): Nishitani C., Takahashi M., et al.
  • Journal Title: Int.Immunol. 21 Pages: 925-934
  • Peer Reviewed
• [Journal Article] Mannose binding lectin and lung collectins interact with Toll-like receptor 4 and MD-2 by different mechanisms. (2009)
  • Author(s): Shimizu T., et al.
  • Journal Title: Biochim.Biophys.Acta. 1790 Pages: 1705-1710
  • Peer Reviewed
• [Presentation] Inhibition of heregulin signaling by N-glycan deleted soluble ErbB3 (2011)
  • Author(s): Takahashi M.
  • Organizer: 2011 Winter Annual Meeting of the Korean Society for Glycoscience
  • Place of Presentation: Daejeon Conference Hall(韓国)
  • Year and Date: 2011-01-28
• [Presentation] The role of aldehyde reductase in biosynthesis of ascorbic acid in mice (2011)
  • Author(s): Takahashi M., et al.
  • Organizer: International Symposium on Free Radical Research : Contribution to Medicine
  • Place of Presentation: 京都ハイアットリージェンシーホテル(京都市)
  • Year and Date: 2011-01-21
• [Presentation] Inhibition of heregulin signaling by N-glycan deleted soluble ErbB3 (2011)
  • Author(s): Takahashi M., Wada Y., Tajiri M., Yamaguchi Y., Nishitani C., Ariki S., Taniguchi N., Kuroki K.
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都市
• [Presentation] 酸化還元酵素アルデヒドレダクターゼノックアウトマウスで発症するアスコルビン酸欠乏症とその影響 (2011)
  • Author(s): 高橋素子、宮田哲、藤井順逸、井内陽子、上山茂充、曽我朋義、藤縄玲子、荒木素子、谷口直之、黒木由夫
  • Organizer: 第64回日本酸化ストレス学会
  • Place of Presentation: 留寿都町
• [Presentation] Inhibition of heregulin signaling by N-glycan deleted soluble ErbB3 (2011)
  • Author(s): Takahashi M., Wada Y., Tajiri M., Araki M., Yamaguchi Y., Taniguchi N., Kuroki Y.
  • Organizer: 2011 Winter Annual Meeting of the Korean Society for Glycoscience
  • Place of Presentation: Daejeon, Korea
• [Presentation] The role of aldehyde reductase in biosynthesis of ascorbic acid in mice (2011)
  • Author(s): Takahashi M., Miyata S., Fujii J., Ueyama S., Araki M., Soga T., Fujinawa R., Taniguchi N., Kuroki Y.
  • Organizer: International Symposium on Free Radical Research : Contribution to Medicine
  • Place of Presentation: 京都市
• [Presentation] The involvement of aldehyde reductase in biosynthesis of ascorbic acid in mice (2010)
  • Author(s): 高橋素子
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 2010-12-10
• [Presentation] Inhibition of heregulin signaling by N-glycan deleted mutant of sErbB3 (2010)
  • Author(s): 高橋素子
  • Organizer: GlycoT 2010 : The International Symposium on Glycosyl transferases
  • Place of Presentation: 両国(墨田区)
  • Year and Date: 2010-07-31
• [Presentation] The involvement of aldehyde reductase in biosynthesis of ascorbic acid in mice (2010)
  • Author(s): Takahashi M., Fujii J., Araki M., Inai Y., Soga T., Miyata S., Taniguchi N., Kuroki Y.
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸市
• [Presentation] Inhibition of heregulin signaling by N-glycan deleted mutant of sErbB3 GlycoT 2010 (2010)
  • Author(s): Takahashi M., Wada Y., Tajiri M., Araki M., Yamaguchi Y., Taniguchi N., Kuroki Y.
  • Organizer: The 7th International Symposium on Glycosyltransferases
  • Place of Presentation: 墨田区
• [Presentation] The role of aldehyde reductase in biosynthesis of ascorbic acid in mice. (2009)
  • Author(s): 高橋素子
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2009-10-22
• [Presentation] ErbB3のN型糖鎖の構造と機能 (2009)
  • Author(s): 高橋素子
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Place of Presentation: 大阪大学(大阪府)
  • Year and Date: 2009-09-18
• [Presentation] The role of aldehyde reductase in biosynthesis of ascorbic acid in mice (2009)
  • Author(s): Takahashi M., Inai Y., Miyata S., Nishikimi M., Riki S., Taniguchi N., Kuroki Y.
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸市
• [Presentation] ErbBファミリーのN型糖鎖:構造と機能 (2009)
  • Author(s): 高橋素子
  • Organizer: 第7回糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 吹田市
• [Presentation] ErbB3のN型糖鎖の構造と機能 (2009)
  • Author(s): 高橋素子
  • Organizer: 大阪大学蛋白質研究所セミナー「蛋白質修飾:新たな癌の診断・治療標的」
  • Place of Presentation: 吹田市
• [Book] 運動と免疫-からだをまもる運動のふしぎ (2009)
  • Author(s): 高橋素子
  • Publisher: NAP
• [Book] 運動と免疫 (2009)
  • Author(s): 大野秀樹・木崎節子 編著
  • Total Pages: 420
  • Publisher: NAP
• [Remarks]
  • URL: http://web.sapmed.ac.jp/biochem1/index.html
• [Remarks]
  • URL: http://web.sapmed.ac.jp/biocheml/index.html