Regulation of ErbB receptors by N-glycans

• Project/Area Number: 26440058
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• 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): ARIKI Shigeru 札幌医科大学, 医学部, 准教授 (80464478) ; WADA Yoshinao 地方独立行政法人大阪府立病院機構, 大阪府立母子保健総合医療センター, 研究所長 (00250340)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: N型糖鎖 / 糖鎖生物学 / 糖タンパク質 / 増殖因子受容体 / EGFR / ErbB受容体 / 糖鎖 / レセプター / ErbB

Outline of Final Research Achievements

The fundamental role of the glycan chain is to modify the physicochemical properties of target molecules. The aim of this study is to determine the mechanisms by which N-glycans regulate the function and structure of ErbB. First, we improved the purification efficiency of recombinant soluble ErbB (sErbB) over 100-fold. It was observed that the sEGFR N418Q N-glycan deletion mutant suppressed EGF signaling more effectively than the wild type. The crystal structure of the sErbB3 N418Q N-glycan deletion mutant revealed that the static structure of sErbB3 is not altered by the deletion of the N-glycan. In contrast, the thermostability of sErbB3 N418Q was reduced compared to the wild type. These results indicate that the N-glycan on N418 of ErbB3 is involved in the conformational stability of sErbB3, and the deletion of the N-glycan would increase the flexibility of the molecule.

Research Products

• [Journal Article] Surfactant protein A inhibits growth and adherence of uropathogenic Escherichia coli to protect the bladder from infection. (2017)
  • Author(s): Hashimoto J., Takahashi M., Satio A., Murata M., Kurimura Y., Nishitani C., Takamiya R., Uehara Y., Hasegawa Y., Hiyama Y., Sawada N., Takahashi S., Masumori N., Kuroki Y., Ariki S.
  • Journal Title: J. Immunol. Volume: 198 Issue: 7 Pages: 2898-2905
  • DOI: 10.4049/jimmunol.1502626
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Surfactant Protein A (SP-A) and SP-A-derived Peptide Attenuate Chemotaxis of Mast Cells Induced by Human β-defensin 3. (2017)
  • Author(s): Uehara Y., Takahashi M., Murata M., Saito A., Takamiya R., Hasegawa Y., Kuronuma K., Chiba H., Hashimoto J., Sawada N., Takahashi H., Kuroki Y., Ariki S.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 485 Issue: 1 Pages: 107-112
  • DOI: 10.1016/j.bbrc.2017.02.028
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SP-Dによる変異型EGFR肺がんの制御機構 (2017)
  • Author(s): 長谷川喜弘、梅田泰淳、大塚満雄、有木茂、高宮里奈、齋藤充史、黒沼幸治、千葉弘文、高橋弘毅、黒木由夫、高橋素子
  • Journal Title: 分子呼吸器病 Volume: 21 Pages: 80-83
• [Journal Article] Disease-associated glycans on cell surface proteins. (2016)
  • Author(s): Takahashi M, Kizuka Y, Ohtsubo K, Gu J, Taniguchi N.
  • Journal Title: Molecular Aspects of Medicine Volume: 51 Pages: 56-70
  • DOI: 10.1016/j.mam.2016.04.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glycation vs. Glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease. (2016)
  • Author(s): Taniguchi N.*, Takahashi M.*, Kizuka Y., Kitazume S., Shuvaev VV., Ookawara T., Furuta A.
  • Journal Title: Glycoconj. J. Volume: 33 Pages: 487-497
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] N-glycans of growth factor receptors: their role in receptor function and disease implications. (2016)
  • Author(s): Takahashi M, Hasegawa Y, Gao C, Kuroki Y, Taniguchi N.
  • Journal Title: Clinical Science Volume: 130 Issue: 20 Pages: 1781-1792
  • DOI: 10.1042/cs20160273
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling. (2015)
  • Author(s): Hasegawa Y., Takahashi M.*, Ariki S., Asakawa D., Tajiri M., Wada Y., Yamaguchi Y., Nishitani C., Takamiya R., Saito A., Uehara Y., Hashimoto J., Kurimura Y., Takahashi H., Kuroki Y.
  • Journal Title: Oncogene Volume: 34 Issue: 32 Pages: 838-845
  • DOI: 10.1038/onc.2015.266
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fucosylated surfactant protein-D is a biomarker candidate for the development of chronic obstructive pulmonary disease. (2015)
  • Author(s): Ito E., Oka R., Ishi T., Korekane H., Kurimoto A., Kizuka Y., Kitazume S., Ariki S., Takahashi M., Kuroki Y., Kida K., Taniguchi N.
  • Journal Title: Journal of Proteomics Volume: 127 Pages: 386-394
  • DOI: 10.1016/j.jprot.2015.07.011
  • Peer Reviewed
• [Journal Article] 肺サーファクタント蛋白質のEGFシグナル制御を介した抗腫瘍作用 (2015)
  • Author(s): 長谷川喜弘、高橋素子、有木茂、高宮里奈、上原康昭、橋本次朗、和田義直、高橋弘毅、黒木由夫
  • Journal Title: 分子呼吸器病 Volume: 19 Pages: 107-111
• [Journal Article] 肺サーファクタントタンパク質SP-Dによる肺癌の進展の抑制 (2015)
  • Author(s): 高橋素子、長谷川喜弘、黒木由夫
  • Journal Title: Lung Perspective Volume: 23 Pages: 65-69
• [Journal Article] A circadian clock gene, Rev-erbα, modulates the inflammatory function of macrophages through the negative regulation of Ccl2 expression. (2014)
  • Author(s): Sato S, Sakurai T, Ogasawara J, Takahashi M, Izawa T, Imaizumi K, Taniguchi N, Ohno H, Kizaki T.
  • Journal Title: J Immunol. Volume: 192 Issue: 1 Pages: 407-417
  • DOI: 10.4049/jimmunol.1301982
  • Peer Reviewed / Open Access
• [Journal Article] Ascorbic acid neutralizes prolonged anesthetic action of pentobarbital in Akr1a-knockout mice. (2014)
  • Author(s): Ito J., Otsuki N., Zhang X., Konno T., Kurahashi T., Takahashi M., Matsuoka Y., Yamada K., Miyata S., Fujii J.
  • Journal Title: Life Sciences Volume: 95 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals (2014)
  • Author(s): Toshihiro Kurahashi a, Myoungsu Kwona, Takujiro Hommaa, Yuka Saito a, Jaeyong Lee a, Motoko Takahashi b, Ken-ichi Yamadac, Satoshi Miyata d, Junichi Fujii
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 452 Issue: 1 Pages: 136-141
  • DOI: 10.1016/j.bbrc.2014.08.072
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The single N-glycan deletion mutant of soluble ErbB3 protein attenuates heregulinβ1-induced tumor progression by blocking of the HIF-1 and Nrf2 pathway. (2014)
  • Author(s): Takamiya R, Takahashi M, Uehara Y, Ariki S, Hashimoto J, Hasegawa Y, Kuroki Y
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 454 Issue: 3 Pages: 364-368
  • DOI: 10.1016/j.bbrc.2014.10.086
  • Peer Reviewed / Open Access
• [Journal Article] 肺サーファクタントの感染・炎症防御における役割 (2014)
  • Author(s): 高橋素子、有木茂、黒木由夫
  • Journal Title: 呼吸器内科 Volume: 16 Pages: 121-124
• [Presentation] 糖鎖改変・可溶型EGFR によるEGFシグナル抑制作用のメカニズム (2016)
  • Author(s): 高橋素子、長谷川喜弘、加藤公児、姚閔、和田芳直、有木茂、高宮里奈、齋藤充史、黒木由夫
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-09-25
• [Presentation] EGFRのN型糖鎖の機能 (2016)
  • Author(s): 高橋素子、長谷川喜弘、和田芳直、加藤公児、姚閔、有木茂、高宮里奈、齋藤充史、黒木由夫
  • Organizer: 第35回日本糖質学会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知県高知市）
  • Year and Date: 2016-09-01
• [Presentation] 糖鎖改変・可溶型ErbB3 による抗腫瘍作用の分子メカニズム (2015)
  • Author(s): 高橋素子、加藤公児、姚閔、和田芳直、田尻道子、長谷川喜弘、高宮里奈、有木茂黒木由夫
  • Organizer: 第88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: 2015-12-01
• [Presentation] EGFRのドメインIIIの糖鎖による機能制御 (2015)
  • Author(s): 高橋素子、長谷川喜弘、高宮里奈、和田芳直、田尻道子、浅川大樹、有木茂、黒木由夫
  • Organizer: 第34回日本糖質学会
  • Place of Presentation: 東京大学（東京都文京区）
  • Year and Date: 2015-07-31
• [Presentation] 肺サーファクタントタンパク質SP-Dの機能 (2015)
  • Author(s): 高橋素子、長谷川喜弘、高宮里奈、有木茂、高橋弘毅、黒木由夫
  • Organizer: 第34回気道分泌学会
  • Place of Presentation: 札幌プリンスホテル（札幌市）
  • Year and Date: 2015-07-11
  • Invited
• [Presentation] Signaling-inhibitory effects of sErbB3 is enhanced by single N-glycan deletion. (2014)
  • Author(s): Takahashi M., Hasegawa Y., Ikeda Y., Wada Y., Tajiri M., Ariki S, Takamiya R., Yamaguchi Y., Taniguchi N., Kuroki Y.
  • Organizer: Joint Meeting of the Society for Glycobiology (SFG) & Japanese Society of Carbohydrate Research (JSCR)
  • Place of Presentation: Honolulu, Hawaii.
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] N型糖鎖によるErbB受容体の機能制御メカニズム (2014)
  • Author(s): 高橋素子, 黒木由夫
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-15 – 2014-10-18
• [Book] Glycoscience: Biology and Medicine (2015)
  • Author(s): Takahashi M.
  • Total Pages: 1568
  • Publisher: Springer-Verlag Tokyo
• [Book] Glycosciences: Biology and Medicine (2015)
  • Author(s): Takahashi M.
  • Total Pages: 1568
  • Publisher: Springer-Verlag Tokyo