Updated on 2024/02/28

写真a

 
OKAJIMA, Tetsuya
 
Organization
Institute for Glyco-core Research Professor
Graduate School of Medicine Professor
Graduate School
Graduate School of Medicine
Title
Professor
Contact information
メールアドレス

Degree 1

  1. 博士(医学) ( 2000.3   名古屋大学 ) 

Research Interests 1

  1. Protein domain-specific glycans

Research Areas 1

  1. Others / Others  / Biochemistry

Current Research Project and SDGs 2

  1. 新型糖鎖による生体機能制御機構

  2. 糖鎖によるNotchシグナルの制御

Research History 10

  1. Nagoya University   Professor

    2021.1

  2. Nagoya University   Institute of Liberal Arts and Sciences

    2018.4

  3. Nagoya University   Institute for Advanced Research

    2016.10

  4. 名古屋大学大学院   医学系研究科   教授

    2015.11

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    Country:Japan

  5. Nagoya University   Graduate School of Medicine Program in Integrated Medicine Biological Chemistry   Professor

    2015.11

  6. 名古屋大学大学院医学系研究科准教授

    2009.10

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    Country:Japan

  7. 名古屋大学大学院医学系研究科講師

    2008.4 - 2009.9

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    Country:Japan

  8. 名古屋大学大学院生命農学研究科応用生命化学講座(分子生体制御学) 助教

    2007.4 - 2008.3

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    Country:Japan

  9. 名古屋大学大学院生命農学研究科応用生命化学講座(分子生体制御学)助手

    2005.12 - 2007.3

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    Country:Japan

  10. 名古屋大学医学部非常勤講師

    2005.6 - 2005.12

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    Country:Japan

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Education 2

  1. Nagoya University

    1996.4 - 2000.2

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1990.4 - 1996.3

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    Country: Japan

Professional Memberships 3

  1. 日本生化学会

  2. 日本糖質学会

  3. 日本分子生物学会

Awards 4

  1. 日本糖質学会奨励賞

    2009  

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    Country:Japan

  2. Career Development Award

    2006   Human Frontier Science Program  

  3. JB/OUPポスター賞

    2009   日本生化学会/オックスフォード大学出版局  

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    「細胞外O-GlcNAc修飾機構の生化学的解析」

  4. 日本生化学会奨励賞

    2010  

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    Country:Japan

 

Papers 105

  1. Characterization of galactosyltransferase and sialyltransferase genes mediating the elongation of the extracellular O-GlcNAc glycans.

    Tsukamoto Y, Tsukamoto N, Saiki W, Tashima Y, Furukawa JI, Kizuka Y, Narimatsu Y, Clausen H, Takeuchi H, Okajima T

    Biochemical and biophysical research communications   Vol. 703   page: 149610   2024.2

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    DOI: 10.1016/j.bbrc.2024.149610

    PubMed

  2. Inhibitory machinery for the functional dystroglycan glycosylation

    Kondo, Y; Okajima, T

    JOURNAL OF BIOCHEMISTRY   Vol. 173 ( 5 ) page: 333 - 335   2023.5

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  3. Evidence that only EWS among the FET proteins acquires a low partitioning property for the hyperosmotic stress response by O-GlcNAc glycosylation on its low-complexity domain

    Kakuo, M; Horii, T; Tonomura, N; Sato, R; Ogawa, M; Okajima, T; Kamemura, K

    EXPERIMENTAL CELL RESEARCH   Vol. 424 ( 1 ) page: 113504   2023.3

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  4. Secretory expression of mammalian NOTCH tandem epidermal growth factor-like repeats based on increased O-glycosylation

    Zhang, AL; Tsukamoto, Y; Takeuchi, H; Nishiwaki, K; Tashima, Y; Okajima, T

    ANALYTICAL BIOCHEMISTRY   Vol. 656   page: 114881   2022.11

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  5. Roles of POFUT1 and POGLUT1 for the effective transport of DLK1 to the cell surface

    Tashima, Y; Goto, W; Tsukamoto, Y; Ogawa, M; Takeuchi, H; Okajima, T

    GLYCOBIOLOGY   Vol. 32 ( 11 ) page: 1002 - 1003   2022.10

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  6. 3′-Sialyllactose on Notch: Notch1 functions as a scaffold of O-linked, 3′-sialyllactosylated glycans

    Tsukamoto, Y; Aoki, K; Narimatsu, Y; Urata, Y; Saiki, W; Tiemeyer, M; Clausen, H; Kurebayashi, Y; Minami, A; Takahashi, T; Okajima, T; Takeuchi, H

    GLYCOBIOLOGY   Vol. 32 ( 11 ) page: 1022 - 1022   2022.10

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  7. Glycoproteomics of NOTCH1 EGF repeat fragments overexpressed with different glycosyltransferases in HEK293T cells reveals insights into O-GlcNAcylation of NOTCH1

    Tsukamoto, Y; Ogawa, M; Yogi, K; Tashima, Y; Takeuchi, H; Okajima, T

    GLYCOBIOLOGY   Vol. 32 ( 7 ) page: 616 - 628   2022.6

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  8. Significant Roles of Notch <i>O</i>-Glycosylation in Cancer

    Wang, WW; Okajima, T; Takeuchi, H

    MOLECULES   Vol. 27 ( 6 )   2022.3

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  9. Ganglioside GD2 enhances malignant properties of melanoma by co-operating with integrin.

    Farhana, Y; Bhuiyan, RH; Ohmi, Y; Horiuchi, M; Okajima, T; Yamamoto, S; Furukawa, K; Furukawa, K

    CANCER SCIENCE   Vol. 113   page: 1104 - 1104   2022.2

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    Web of Science

  10. Unique effects of expression of asialo-series ganglioside GD1alpha in human cancer cell lines

    Robiul, B; Yesmin, F; Kondo, Y; Ohkawa, Y; Ohmi, Y; Zhang, P; Okajima, T; Furukawa, K; Furukawa, K

    CANCER SCIENCE   Vol. 113   page: 379 - 379   2022.2

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  11. Eogt-catalyzed O-GlcNAcylation

    Lo, PW; Okajima, T

    TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY   Vol. 34 ( 197 ) page: E1 - E6   2022.1

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    DOI: 10.4052/tigg.2033.1E

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  12. Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins

    Yesmin, F; Bhuiyan, RH; Ohmi, Y; Yamamoto, S; Kaneko, K; Ohkawa, Y; Zhang, P; Hamamura, K; Cheung, NKV; Kotani, N; Honke, K; Okajima, T; Kambe, M; Tajima, O; Furukawa, K; Furukawa, K

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 23 ( 1 )   2022.1

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  13. Other Classes of Eukaryotic Glycans

    Haltiwanger RS, Wells L, Freeze HH, Jafar-Nejad H, Okajima T, Stanley P, Varki A, Cummings RD, Esko JD, Stanley P, Hart GW, Aebi M, Mohnen D, Kinoshita T, Packer NH, Prestegard JH, Schnaar RL, Seeberger PH

        2022

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    DOI: 10.1101/glycobiology.4e.13

    PubMed

  14. St8sia1-deficiency in mice alters tumor environments of gliomas, leading to reduced disease severity Reviewed

    Thane, P; Ohkawa, Y; Yamamoto, S; Momota, H; Kato, A; Kaneko, K; Natsume, A; Farhana, Y; Ohmi, Y; Okajima, T; Bhuiyan, RH; Wakabayashi, T; Furukawa, K; Furukawa, K

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 83 ( 3 ) page: 535 - 549   2021.8

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  15. Majority of alpha2,6-sialylated glycans in the adult mouse brain exist in <i>O</i>-glycans: SALSA-MS analysis for knockout mice of alpha2,6-sialyltransferase genes Reviewed

    Ohmi, Y; Nishikaze, T; Kitaura, Y; Ito, T; Yamamoto, S; Sugiyama, F; Matsuyama, M; Takahashi, Y; Takeda, A; Kawahara, T; Okajima, T; Furukawa, K; Furukawa, K

    GLYCOBIOLOGY   Vol. 31 ( 5 ) page: 557 - 570   2021.5

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  16. Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and <i>L</i>-fringe in Pancreatic Cancers Reviewed

    Barua, R; Mizuno, K; Tashima, Y; Ogawa, M; Takeuchi, H; Taguchi, A; Okajima, T

    MOLECULES   Vol. 26 ( 4 )   2021.2

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  17. Current Views on the Roles of <i>O</i>-Glycosylation in Controlling Notch-Ligand Interactions Reviewed

    Saiki, W; Ma, CY; Okajima, T; Takeuchi, H

    BIOMOLECULES   Vol. 11 ( 2 )   2021.2

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  18. Roles of asialo-series ganglioside GD1α in human cancer cell lines. Reviewed

    Bhuiyan, RH; Yesmin, F; Kondo, Y; Ohkawa, Y; Ohmi, Y; Zhang, P; Okajima, T; Furukawa, K; Furukawa, K

    CANCER SCIENCE   Vol. 112   page: 679 - 679   2021.2

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  19. Ganglioside GD2 enhances malignant properties of melanoma by co-operating with integrin. Reviewed

    Yesmin, F; Bhuiyan, RH; Ohmi, Y; Okajima, T; Yamamoto, S; Furukawa, K; Furukawa, K

    CANCER SCIENCE   Vol. 112   page: 699 - 699   2021.2

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  20. Enzyme assay of O-GlcNAc transferase.

    Nishihara S, Angata K, Aoki-Kinoshita KF, Hirabayashi J, Alam SMD, Okajima T

        2021

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  21. Enzyme assay of O-fucosyltransferase 1 using Drosophila OFUT1.

    Nishihara S, Angata K, Aoki-Kinoshita KF, Hirabayashi J, Okajima T

        2021

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  22. 3′-Sialyllactose on Notch: NOTCH1 functions as a scafold of O-linked, 3′-sialyllactosylated glycans

    Tsukamoto, Y; Aoki, K; Narimatsu, Y; Urata, Y; Saiki, W; Ogawa, M; Clausen, H; Tiemeyer, M; Okajima, T; Takeuchi, H

    GLYCOBIOLOGY   Vol. 30 ( 12 ) page: 1119 - 1120   2020.12

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  23. N-glycans on EGF domain-specific O-GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization

    Alam, SMD; Tsukamoto, Y; Ogawa, M; Senoo, Y; Ikeda, K; Tashima, Y; Takeuchi, H; Okajima, T

    GLYCOBIOLOGY   Vol. 30 ( 12 ) page: 1031 - 1032   2020.12

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  24. Comprehensive O-GlcNAc glycoproteomics on NOTCH1 EGF repeats refined the sequons for O-GlcNAcylation and uncovered unique Lewis X epitopes in mammals

    Ogawa, M; Tsukamoto, Y; Yogi, K; Senoo, Y; Ikeda, K; Takeuchi, H; Okajima, T

    GLYCOBIOLOGY   Vol. 30 ( 12 ) page: 1086 - 1087   2020.12

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  25. Glycoproteomic analysis identifies cryptdin-related sequence 1 as <i>O</i>-glycosylated protein modified with α1,2-fucose in the small intestine Reviewed

    Hashiguchi, H; Tsukamoto, Y; Ogawa, M; Tashima, Y; Takeuchi, H; Nakamura, M; Kawashima, H; Fujishiro, M; Okajima, T

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   Vol. 695   page: 108653   2020.11

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    DOI: 10.1016/j.abb.2020.108653

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  26. Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs Reviewed

    Ma Chenyu, Takeuchi Hideyuki, Hao Huilin, Yonekawa Chizuko, Nakajima Kazuki, Nagae Masamichi, Okajima Tetsuya, Haltiwanger Robert S., Kizuka Yasuhiko

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 21 ( 17 )   2020.9

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    DOI: 10.3390/ijms21176007

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  27. Aminoglycosides are efficient reagents to induce readthrough of premature termination codon in mutant B4GALNT1 genes found in families of hereditary spastic paraplegia.

    Yesmin F, Bhuiyan RH, Ohmi Y, Ohkawa Y, Tajima O, Okajima T, Furukawa K, Furukawa K

    Journal of biochemistry   Vol. 168 ( 2 ) page: 103 - 112   2020.8

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    DOI: 10.1093/jb/mvaa041

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  28. N-Glycans on EGF domain-specificO-GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization

    Alam Sayad Md. Didarul, Tsukamoto Yohei, Ogawa Mitsutaka, Senoo Yuya, Ikeda Kazutaka, Tashima Yuko, Takeuchi Hideyuki, Okajima Tetsuya

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 295 ( 25 ) page: 8560 - 8574   2020.6

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    DOI: 10.1074/jbc.RA119.012280

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  29. Contribution of extracellular O-GlcNAc to the stability of folded epidermal growth factor-like domains and Notch1 trafficking

    Ogawa Mitsutaka, Tashima Yuko, Sakaguchi Yamato, Takeuchi Hideyuki, Okajima Tetsuya

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 526 ( 1 ) page: 184 - 190   2020.5

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    DOI: 10.1016/j.bbrc.2020.03.066

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  30. Xylosyl Extension of O-Glucose Glycans on the Extracellular Domain of NOTCH1 and NOTCH2 Regulates Notch Cell Surface Trafficking

    Urata Yusuke, Saiki Wataru, Tsukamoto Yohei, Sago Hiroaki, Hibi Hideharu, Okajima Tetsuya, Takeuchi Hideyuki

    CELLS   Vol. 9 ( 5 )   2020.5

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    DOI: 10.3390/cells9051220

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  31. The ceramide moiety of disialoganglioside (GD3) is essential for GD3 recognition by the sialic acid-binding lectin SIGLEC7 on the cell surface

    Hashimoto Noboru, Ito Shizuka, Tsuchida Akiko, Bhuiyan Robiul H., Okajima Tetsuya, Yamamoto Akihito, Furukawa Keiko, Ohmi Yuhsuke, Furukawa Koichi

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 294 ( 28 ) page: 10833 - 10845   2019.7

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    DOI: 10.1074/jbc.RA118.007083

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  32. Extracellular O-GlcNAc: From Discovery to Current Developments

    Okajima Tetsuya

    TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY   Vol. 31 ( 181 ) page: SE57 - SE58   2019.7

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    DOI: 10.4052/tigg.1927.2SE

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  33. Structure and function of extracellular <i>O</i>-GlcNAc

    Ogawa, M; Okajima, T

    CURRENT OPINION IN STRUCTURAL BIOLOGY   Vol. 56   page: 72 - 77   2019.6

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  34. Loss of Enzyme Activity in Mutated B4GALNT1 Gene Products in Patients with Hereditary Spastic Paraplegia Results in Relatively Mild Neurological Disorders: Similarity with Phenotypes of B4galnt1 Knockout Mice

    Bhuiyan Robiul H., Ohmi Yuhsuke, Ohkawa Yuki, Zhang Pu, Takano Maiko, Hashimoto Noboru, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    NEUROSCIENCE   Vol. 397   page: 94 - 106   2019.1

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    DOI: 10.1016/j.neuroscience.2018.11.034

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  35. Structure and function of extracellular O-GlcNAc Invited Reviewed

    Mitsutaka Ogawa, Tetsuya Okajima

    Current Opinion in Structural Biology   Vol. 56   page: 72-77   2019

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  36. Significant roles of O-glucose glycans in mammalian Notch trafficking and signaling

    Takeuchi, H; Yu, HJ; Hao, HL; Urata, Y; Senoo, Y; Tsukamoto, Y; Saiki, W; Takeuchi, M; Ito, A; Li, HL; Okajima, T; Haltiwanger, RS

    GLYCOBIOLOGY   Vol. 28 ( 12 ) page: 1017 - 1018   2018.12

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  37. Exploring the significance of xylosyl-extension of O-glucose glycans on EGF repeats for Notch signaling in mammals

    Saiki, W; Urata, Y; Senoo, Y; Tsukamoto, Y; Ma, CY; Okajima, T; Takeuchi, H

    GLYCOBIOLOGY   Vol. 28 ( 12 ) page: 1028 - 1029   2018.12

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  38. Roles of asialo-series ganglioside GD1alpha in human cancer cell lines

    Bhuiyan, RH; Kondo, Y; Ohkawa, Y; Ohmi, Y; Zhang, P; Okajima, T; Furukawa, K; Furukawa, K

    CANCER SCIENCE   Vol. 109   page: 877 - 877   2018.12

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  39. Roles of ganglioside GD3 in the regulation of microenvironment of gliomas

    Zhang, P; Ohkawa, Y; Ohmi, Y; Robiul, HB; Kato, A; Furukawa, K; Okajima, T; Wakabayashi, T; Furukawa, K

    CANCER SCIENCE   Vol. 109   page: 262 - 262   2018.12

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  40. Whole mount staining of retina

    Mitsutaka Ogawa, Tetsuya Okajima

    bio-101   Vol. 8 ( 19 ) page: e3034   2018.10

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    DOI: 10.21769/BioProtoc.3034

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  41. Isolation of Murine Brain and Lung Microvascular Endothelial Cells Invited Reviewed

    Ailing Zhang, Shogo Sawaguchi, Entzu Wan, Mitsutaka Ogawa, Tetsuya Okajima

    bio-101     2018.8

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    DOI: 10.21769/BioProtoc.2984

  42. Congenital diseases caused by defective O-glycosylation of Notch receptors

    Tashima Yuko, Okajima Tetsuya

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 80 ( 3 ) page: 299 - 307   2018.8

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    DOI: 10.18999/nagjms.80.3.299

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  43. Structural Divergence in <i>O</i>-GlcNAc Glycans Displayed on Epidermal Growth Factor-like Repeats of Mammalian Notch1.

    Ogawa M, Senoo Y, Ikeda K, Takeuchi H, Okajima T

    Molecules (Basel, Switzerland)   Vol. 23 ( 7 )   2018.7

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    DOI: 10.3390/molecules23071745

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  44. NOTCH SIGNALING A sweet strategy

    Okajima Tetsuya

    NATURE CHEMICAL BIOLOGY   Vol. 14 ( 1 ) page: 3 - 4   2018.1

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    DOI: 10.1038/nchembio.2532

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  45. Ganglioside GD3/GD2 enhance malignant properties of human glioma U251 cells

    Zhang, P; Iwasawa, T; Ohkawa, Y; Bhuiyan, RH; Momota, H; Wakabayashi, T; Ohmi, Y; Okajima, T; Furukawa, K; Furukawa, K

    CANCER SCIENCE   Vol. 109   page: 256 - 256   2018.1

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  46. Protocol for Notch-ligand Binding Assays Using Dynabeads Invited Reviewed

    bio-protocol     2017.10

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    DOI: 10.21769/BioProtoc.2582

  47. O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals

    Sawaguchi Shogo, Varshney Shweta, Ogawa Mitsutaka, Sakaidani Yuta, Yagi Hirokazu, Takeshita Kyosuke, Murohara Toyoaki, Kato Koichi, Sundaram Subha, Stanley Pamela, Okajima Tetsuya

    ELIFE   Vol. 6   2017.4

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    DOI: 10.7554/eLife.24419

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  48. Neogenin defined as a GD3-associated molecule by enzyme-mediated activation of radical sources confers malignant properties via intra-cytoplasmic domain in melanoma cells.  Reviewed

    Kaneko K, Ohkawa Y, Hashimoto N, Ohmi Y, Kotani N, Honke K, Ogawa M, Okajima T, Furukawa K, Furukawa K

    J. Biol. Chem.   Vol. 291   page: 16630-16643   2016

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  49. Impaired O-linked N-acetylglucosaminylation in the endoplasmic reticulum by mutated EGF domain-specific O-linked N-acetylglucosamine transferase found in Adams-Oliver syndrome.

    Ogawa M, Sawaguchi S, Kawai T, Nadano D, Matsuda T, Yagi H, Kato K, Furukawa K, Okajima T.

    J Biol Chem     page: in press   2015

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  50. O-fucose monosaccharide of Drosophila Notch has a temperature-sensitive function and cooperates with O-glucose glycan in Notch transport and Notch signaling activation. Reviewed

    Ishio A, Sasamura T, Ayukawa T, Kuroda J, Ishikawa HO, Aoyama N, Matsumoto K, Gushiken T, Okajima T, Yamakawa T, Matsuno K.

    J Biol Chem     page: in press   2015

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  51. Extracellular O-linked beta-N-acetylglucosamine: Its biology and relationship to human disease. Invited Reviewed

    Ogawa M, Furukawa K, Okajima T.

    World J Biol Chem   Vol. 5   page: 224-230   2014

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  52. Allergenic potential of rice-pollen proteins: expression, immuno-cross reactivity and IgE-binding.

      Vol. 154   page: 195-205   2013

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  53. Dephosphorylation reduces passage of ovalbumin antigen through intestinal epithelial Caco-2 cell monolayers.

      Vol. 153   page: 347-354   2013

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  54. GTDC2 modifies O-mannosylated α-dystroglycan in the endoplasmic reticulum to generate N-acetyl-glucosamine epitopes reactive with CTD110.6 antibody. Reviewed

      Vol. 440   page: 88-93   2013

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  55. Post-weaning increases in the milk-fat globule EGF-factor VIII on fat globules in mouse milk and in the uptake of the fat globules by HC11 mammary epithelial cells. Reviewed

      Vol. 153   page: 31-41   2013

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  56. Trimeric Tn Antigen on Syndecan 1 Produced by ppGalNAc-T13 Enhances Cancer Metastasis via a Complex Formation with Integrin alpha5beta1 and Matrix Metalloproteinase 9. Reviewed

      Vol. 288   page: 24264-24276   2013

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  57. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1.

      Vol. 419   page: 14-19   2012

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  58. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen. Reviewed

      Vol. 419   page: 7-13   2012

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  59. Discharge of solubilized and Dectin-1-reactive beta-glucan from macrophage cells phagocytizing insoluble beta-glucan particles: Involvement of reactive oxygen species (ROS)-driven degradation. Reviewed

      Vol. 421   page: 329-334   2012

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  60. O-linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions Reviewed

      Vol. 2   page: 583   2011.12

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    DOI: 10.1038

  61. Strong antibody reaction against glycosphingolipids injected in liposome-embedded forms in beta3GN-T5 knockout mice.

      Vol. 73   page: 137-146   2011

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  62. Secretion of three enzymes for fatty acid synthesis into mouse milk in association with fat globules, and rapid decrease of the secreted enzymes by treatment with rapamycin

      Vol. 508   page: 87-92   2011

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  63. Specific O-glycosylation modifying epidermal growth factor domains.

      Vol. 83   page: 813-821   2011

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  64. Establishment of a Mammary Stromal Fibroblastic Cell Line for In Vitro Studies in Mice of Mammary Adipocyte Differentiation. Reviewed

    Nakatani H, Aoki N, Okajima T, Nadano D, Flint D, Matsuda T.

    Biol. Reprod.   Vol. 82   page: 44-53   2010

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  65. O-GlcNAc modification on EGF domains of Notch receptors.

    Sakaidani Y, Furukawa K, Okajima T.

    Methods Enzymol.   Vol. 480   page: 355-73   2010

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  66. Proteomic Analysis of Rodent Ribosomes Revealed Heterogeneity Including Ribosomal Proteins L10-like, L22-like 1, and L39-like. Reviewed

    Sugihara Y, Honda H, Iida T, Morinaga T, Hino S, Okajima T, Matsuda T, Nadano D.

    J. Proteome Res.   Vol. 9   page: 1351-66   2010

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  67. IgG2 dominancy and carbohydrate recognition specificity of C3H/He mouse antibodies directed to cross-reactive carbohydrate determinants (CCDs) bearing ß-(1,2)-xylose and α-(1,3)-fucose

      Vol. 133   page: 28-34   2010

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  68. Identification of heterogeneous nuclear ribonucleoprotein A/B as a cytoplasmic mRNA-binding protein in early involution of the mouse mammary gland.

      Vol. 28   page: 321-328   2010

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  69. Roles of glycosylation in Notch signaling.

      Vol. 92   page: 131-164   2010

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  70. Binding of Norovirus virus-like particles (VLPs) to human intestinal Caco-2 cells and the sup-pressive effect of pasteurized bovine colostrum on this VLP binding.

      Vol. 74   page: 541-547.   2010

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  71. Glycoconjugate glycosyltransferases. Invited Reviewed

    Furukawa K, Tsuchida A, Okajima T, Furukawa K.

    Glycoconj. J.   Vol. 26   page: 987-998   2009

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  72. Periodate-resistant carbohydrate epitopes recognized by IgG and IgE antibodies from some of the immunized mice and patients with allergy. Reviewed

    Hino S, Matsubara T, Urisu A, Aoki N, Sato C, Okajima T, Nadano D, Matsuda T.

    Biochem. Biophys Res. Commun.   Vol. 380   page: 632-637   2009

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  73. Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling Reviewed

    Okajima T, Reddy B, Matsuda T and Irvine KD

    BMC biology   Vol. 6 ( 1 ) page: 1-26   2008.1

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  74. Biological functions of glycosyltransferase genes involved in O-fucose glycan synthesis Invited Reviewed

    Okajima T, Matsuura A, Matsuda T

    J. Biochem.   Vol. 144   page: 1-6   2008

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  75. *O-linked GlcNAc is present on the extracellular domain of Notch receptors. Reviewed

    Matsuura A, Ito M, Sakaidani Y, Kondo T, Murakami K, Furukawa K, Nadano D, Matsuda T, and Okajima T

    J. Biol. Chem.   Vol. 283 ( 51 ) page: 35486-35495   2008

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  76. Glycosyltransferases involved in O-fucose glycan synthesis.

    Okajima T, Matsuda T

    Experimental Glycoscience     page: 33-35   2008

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  77. 糖転移酵素のNotch受容体フォールディングにおける役割

    松浦愛子・松田幹・岡島徹也

    蛋白質核酸酵素   Vol. 53   page: 1480-1485   2008

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  78. Serum and monoclonal IgE antibodies from NC/Nga mice with severe atopic-like dermatitis recognize an autoantigen, histone H3. Reviewed

    Matsubara T, Aoki N, Hino H, Okajima T, Nadano D, Matsuda T

    Clin. Exp. Allergy   Vol. 39   page: 579-590   2008

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  79. Absorption, Migration and Kinetics in Peripheral Blood of Orally Administered Ovalbumin in a Mouse Model Reviewed

    Matsubara T, Aoki N, Honjoh T, Mizumachi K, Kurisaki JI, Okajima T, Nadano D, Matsuda T

    Biosci. Biotechnol. Biochem.   Vol. 72   page: 2555-2565   2008

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  80. Suppressive expression of the glutelin A1-collagen peptide fusion gene in hybrid rice lines with the mutant line, Low Glutelin Content-1 (LGC-1) Reviewed

    Hashizume F, Hino S, Okajima T, Nadano D, Aoki N and Matsuda T

    Plant Biotechnol   Vol. 25   page: 465-471   2008

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  81. Development and evaluation of transgenic rice seeds accumulating a type II-collagen tolerogenic peptide Reviewed

    Hashizume F, Hino S, Kakehashi M, Okajima T , Nadano D, Aoki N, and Matsuda T

    Transgenic Research   Vol. 17   page: 1117-1129   2008

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  82. Glycoconjugate glycosyltransferases Invited Reviewed

    Furukawa K, Tsuchida A, Okajima T, Furukawa K

    Glycoconj. J   Vol. 26   page: 987-98   2008

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  83. Engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisiae: production of O-fucosylated epidermal growth factor domains Reviewed

    Yuko Chigira, Takuji Oka, Tetsuya Okajima and Yoshifumi Jigami

    Glycobiology   Vol. 18   page: 303-314   2008

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  84. Association of chicken zona pellucida glycoprotein (ZP) B1 with ZPC induces formation of ZPB1-ZPC fibrous aggregates containing disulfide-bridged ZPB1 dimer. Reviewed

    Okumura H, Okajima T, Nadano D, Matsuda T.

    Biochem Biophys Res Commun.   Vol. 364 ( 3 ) page: 682-688   2007.12

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  85. Bystin in human cancer cells: intracellular localization and function in ribosome biogenesis. Reviewed

    Miyoshi M, Okajima T, Matsuda T, Fukuda MN, Nadano D.

    Biochem J   Vol. 404 ( 3 ) page: 373-381   2007.6

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  86. Roles of fucosyltransferase and fucose in Notch signaling Invited

    Okajima T, Matuda T.

    Methods Enzymol   Vol. 417   page: 116-26   2006

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  87. *Chaperone activity of protein O-fucosyltransferase 1 promotes notch receptor folding. Reviewed

    Okajima T, Xu A, Lei L, Irvine KD.

    Science   Vol. 307   page: 1599-603   2005.3

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    Notch proteins are receptors for a conserved signaling pathway that affects numerous cell fate decisions. We found that in Drosophila, Protein O-fucosyltransferase 1 (OFUT1), an enzyme that glycosylates epidermal growth factor-like domains of Notch, also has a distinct Notch chaperone activity. OFUT1 is an endoplasmic reticulum protein, and its localization was essential for function in vivo. OFUT1 could bind to Notch, was required for the trafficking of wild-type Notch out of the endoplasmic reticulum, and could partially rescue defects in secretion and ligand binding associated with Notch point mutations. This ability of OFUT1 to facilitate folding of Notch did not require its fucosyltransferase activity. Thus, a glycosyltransferase can bind its substrate in the endoplasmic reticulum to facilitate normal folding.

  88. *Modulation of notch-ligand binding by protein O-fucosyltransferase 1 and fringe. Invited Reviewed

    Okajima T, Xu A, Irvine KD.

    J Biol Chem.   Vol. 278   page: 42340-5   2003.10

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  89. Synthesis of disialyl Lewis a (Le(a)) structure in colon cancer cell lines by a sialyltransferase, ST6GalNAc VI, responsible for the synthesis of alpha-series gangliosides. Reviewed

    Tsuchida A, Okajima T, Furukawa K, Ando T, Ishida H, Yoshida A, Nakamura Y, Kannagi R, Kiso M, Furukawa K.

    J Biol Chem.   Vol. 278   page: 22787-94   2003.6

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  90. XGalT-1 involved in the synthesis of glyosaminoglycans of proteoglycans and Ehlers-Danlos syndrome (progeroid type) Invited

    Furukawa K, Okajima T, Nakamura Y.

    Tanpakushitsu Kakusan Koso.   Vol. 48 ( 8 Suppl ) page: 1152-7   2003.1

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  91. *Regulation of notch signaling by O-linked fucose. Invited Reviewed

    Okajima T, Irvine KD.

    Cell   Vol. 111   page: 893-904   2002.12

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  92. Galactosyltransferase I is a gene responsible for progeroid variant of Ehlers-Danlos syndrome: molecular cloning and identification of mutations. Invited

    Furukawa K, Okajima T.

    Biochim Biophys Acta.   Vol. 1573 ( 3 ) page: 377-81   2002.12

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  93. Identification of a Drosophila gene encoding xylosylprotein beta4-galactosyltransferase that is essential for the synthesis of glycosaminoglycans and for morphogenesis. Reviewed

    Nakamura Y, Haines N, Chen J, Okajima T, Furukawa K, Urano T, Stanley P, Irvine KD, Furukawa K.

    J Biol Chem.   Vol. 277 ( 48 ) page: 46280-8   2002.11

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  94. b-series Ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apoptosis but impairs regeneration of the lesioned hypoglossal nerve. Reviewed

    Okada M, Itoh Mi M, Haraguchi M, Okajima T, Inoue M, Oishi H, Matsuda Y, Iwamoto T, Kawano T, Fukumoto S, Miyazaki H, Furukawa K, Aizawa S, Furukawa K.

    J Biol Chem.   Vol. 277 ( 3 ) page: 1633-6   2002.1

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  95. Expression cloning of human globoside synthase cDNAs: Identification of β3Gal-T3 as UDP-N-acetylgalactosamine: globotriaosylceramide β1,3-N-acetyl-galactosaminyltransferase. Reviewed

    Okajima T, Nakamura Y, Uchikawa M, Haslam DB, Numata Si, Furukawa K, Urano T, Furukawa K

    J. Biol. Chem.   Vol. 275   page: 40498-40503   2000

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  96. Molecular cloning and expression of mouse GD1α/GT1aα/GQ1bα synthase (ST6GalNAc VI) gene. Reviewed

    Okajima T, Chen HH, Ito H, Kiso M, Tai T, Furukawa K, Urano T, Furukawa K.

    J. Biol. Chem.   Vol. 275   page: 6717-6723   2000

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  97. Molecular cloning of Gb3/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo-series glycosphingolipids. Reviewed

    Kojima Y, Fukumoto S, Furukawa K, Okajima T, Wiels J, Yokoyama K, Suzuki Y, Urano T, Ohta M, Furukawa K.

    J. Biol. Chem.   Vol. 275   page: 15152-15156   2000

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  98. Assignment of human xylosylprotein beta-1,4-galactosyltransferase gene (B4GALT7) to human chromosome 5q35.2-->q35.3 by in situ hybridization. Reviewed

    Kuroiwa A, Matsuda Y, Okajima T, Furukawa K

    Cytogenet. Cell Genet.   Vol. 89   page: 8-9   2000

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  99. Molecular basis for the p phenotype: Identification of distinct and multiple mutations in the α1,4-galactosyltransferase gene in Swedish and Japanese individuals. Reviewed

    Furukawa K, Iwamura K, Uchikawa M, Sojka BN, Wiels J, Okajima T, Urano T, Furukawa K.

    J. Biol. Chem.   Vol. 275   page: 37752-37756   2000

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  100. Molecular cloning of brain-specific GD1α synthase (ST6GalNAc V) containing CAG/Glutamine repeats. Reviewed

    Okajima T, Fukumoto S, Ito H, Kiso M, Hirabayashi Y, Urano T, Furukawa K, Furukawa K.

    J. Biol. Chem   Vol. 274   page: 30557-30562   1999

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  101. Molecular cloning of a novel α2,3-sialyltransferase (ST3Gal VI) that sialylates type II lactosamine structures on glycoproteins and glycolipids. Reviewed

    Okajima T, Fukumoto S, Miyazaki H, Ishida H, Kiso M, Furukawa K, Urano T, Furukawa K.

    J. Biol. Chem.   Vol. 274   page: 11479-11486   1999

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  102. Human homolog of Caenorhabditis elegans sqv-3 gene is galactosyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans. Reviewed

    Okajima T, Yoshida K, Kondo T, Furukawa K.

    J. Biol. Chem.   Vol. 274   page: 22915-22918   1999

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  103. *Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. Identification and characterization of two mutations in galactosyltransferase I gene. Reviewed

    Okajima T, Fukumoto S, Furukawa K, Urano T, Furukawa K.

    J. Biol. Chem.   Vol. 274   page: 28841-28844   1999

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  104. Nuclear localization of Ca2+/calmodulin-dependent protein kinase IV and calspermin. Reviewed

    Okajima T, Okuno S, Fujisawa H, Hagiwara M.

    Bioimages   Vol. 4   page: 117-128   1996

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  105. RNA priming coupled with DNA synthesis on natural template by calf thymus DNA polymerase α-primase. Reviewed

    Suzuki M, Savoysky E, Izuta S, Tatebe M, Okajima T, Yoshida S.

    Biochemistry   Vol. 32   page: 12782-92   1993

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▼display all

Books 12

  1. Glycoscience: Biology and Medicine, Editors: Taniguchi N. et al. Extracellular O-GlcNAcylation

    Ogawa M, Furukawa K, Okajima T.( Role: Sole author)

    Springer  2015 

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  2. Handbook of Glycosyltransferases and Related Gene, Editors: Taniguchi N. et al. ST3 β-galactoside α-2,3-sialyltransferase 6 (ST3GAL6)

    Okajima T, and Furukawa, K.( Role: Joint author)

    Springer  2014 

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  3. Handbook of Glycosyltransferases and Related Gene, Editors: Taniguchi N. et al. ST6 N-acetylgalactosaminide α-2,6-sialyltransferase 5,6 (ST6GALNAC5,6)

    Okajima T, and Furukawa, K( Role: Sole author)

    Springer  2014 

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  4. 第三の生命鎖 糖鎖の機能と疾患 編集 門松健治ら 新たに同定されたO-GlcNAc型ドメイン特異糖鎖と生物学的役割

    河合崇生、古川鋼一、岡島徹也( Role: Sole author)

    羊土社  2013 

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    Language:Japanese

  5. Roles of glycosyltransferases in Notch receptor folding

    Aiko Matsuura, Tsukasa Matsuda, Tetsuya Okajima( Role: Joint author)

    2008 

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  6. Experimental Glycoscience, Editors: Taniguchi, N. et al. Glycosyltransferases involved in O-fucose glycan synthesis.

    Okajima T, Matsuda T.( Role: Joint author)

    Elsevier  2008 

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  7. EGFドメインに見いだされる新型糖鎖と生体機能制御

    岡島徹也( Role: Sole author)

    化学と生物  2006.12 

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  8. 未来を拓く糖鎖科学

    岡島徹也 古川鋼一( Role: Joint author)

    金芳社  2005.12 

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  9. O-フコース型糖鎖によるNotchシグナル制御の分子機構

    岡島徹也( Role: Sole author)

    実験医学  2004 

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  10. O-フコース型糖鎖によるNotchシグナルの制御

    岡島徹也( Role: Sole author)

    医学のあゆみ  2003 

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  11. プロテオグリカンの糖鎖の合成にかかわるXgalT-1とEhlers-Danlos症候群(早老型)

    古川鋼一・岡島徹也・中村陽子( Role: Joint author)

    蛋白質核酸酵素  2003 

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  12. ガングリオシドGD3と増殖・アポトーシスシグナル

    古川鋼一,福本 敏,井上雅博,岡田雅彦,大石秀人,岡島徹也,古川圭子( Role: Joint author)

    細胞工学  2001 

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▼display all

MISC 5

  1. Exploring the significance of xylosyl-extension of O-glucose glycans on EGF repeats for Notch signaling in mammals

    Saiki Wataru, Urata Yusuke, Senoo Yuya, Tsukamoto Yohei, Ma Chenyu, Okajima Tetsuya, Takeuchi Hideyuki

    GLYCOBIOLOGY   Vol. 28 ( 12 ) page: 1028-1029   2018.12

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    Web of Science

  2. Roles of ganglioside GD3 in the regulation of microenvironment of gliomas

    Zhang Pu, Ohkawa Yuki, Ohmi Yuhsuke, Robiul Bhuiyan H., Kato Akira, Furukawa Keiko, Okajima Tetsuya, Wakabayashi Toshihiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 109   page: 262-262   2018.12

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    Web of Science

  3. Significant roles of O-glucose glycans in mammalian Notch trafficking and signaling

    Takeuchi Hideyuki, Yu Hongjun, Hao Huilin, Urata Yusuke, Senoo Yuya, Tsukamoto Yohei, Saiki Wataru, Takeuchi Megumi, Ito Atsuko, Li Huilin, Okajima Tetsuya, Haltiwanger Robert S.

    GLYCOBIOLOGY   Vol. 28 ( 12 ) page: 1017-1018   2018.12

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    Web of Science

  4. Roles of asialo-series ganglioside GD1alpha in human cancer cell lines

    Bhuiyan Robiul H., Kondo Yuji, Ohkawa Yuki, Ohmi Yuhsuke, Zhang Pu, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 109   page: 877-877   2018.12

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    Web of Science

  5. Ganglioside GD3/GD2 enhance malignant properties of human glioma U251 cells

    Zhang Pu, Iwasawa Taiji, Ohkawa Yuki, Bhuiyan R. H., Momota Hiroyuki, Wakabayashi Toshihiko, Ohmi Yuhsuke, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 109   page: 256-256   2018.1

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    Web of Science

Presentations 19

  1. Structure and function of extracellular O-GlcNAc Invited International conference

    Tetsuya Okajima and Mitsutaka Ogawa

    10th ACGG Conference 

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    Event date: 2018.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  2. Notch受容体糖鎖情報トラジェクトリーの理解に向けた細胞外O-GlcNAc修飾の構造機能解析 Invited

    岡島 徹也, 竹内 英之, 小川 光貴

    第91回日本生化学会大会 

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    Event date: 2018.9

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Country:Japan  

  3. O-グルコース糖鎖のキシロシル化の Notch シグナルにおける役割の解析 International conference

    浦田 悠輔, 斎木 颯, 妹尾 勇弥, 竹内 英之, 岡島 徹也, 日比 英晴

    第91回日本生化学会大会 

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    Event date: 2018.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  4. 哺乳動物Notch1の上皮成長因子様リピートを修飾するO-GlcNAc糖鎖の構造多様性

    小川 光貴 、妹尾 勇弥、池田 和貴、竹内 英之 、岡島 徹也

    第37回日本糖質学会年会 

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    Event date: 2018.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  5. O-GlcNAc は Notch 受容体 EGF20 の安定性を増強する International conference

    小川光貴, 坂口大和, 矢木宏和, 加藤晃一, 竹内英之, 岡島徹也

    日本生化学会中部支部第82回例会・シンポジウム 

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    Event date: 2018.5

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  6. Roles of N-Glycans on EGF domain-specific O-GlcNAc transferase (EOGT)-catalyzed Notch1 O-GlcNAcylation and Notch signaling International conference

    Sayad Md. Didarul Alam, Mitsutaka Ogawa, Hideyuki Takeuchi and Tetsuya Okajima

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    Event date: 2018.5

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  7. Roles of ganglioside GD3 in the regulation of microenvironment of gliomas

    Zhang P,Ohkawa Y, Momota H, Wakabayashi T, Ohmi Y, Bhuiyan RH, Furukawa Keiko,Okajima Tetsuya, Furukawa Koichi.

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    Event date: 2017.12

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  8. 細胞外O-GlcNAcの修飾に関わるEOGT変異マウスの表現型解析 International conference

    澤口 翔伍、小川 光貴、矢木 宏和、加藤 晃一、岡島 徹也

    2017年度生命科学系学会合同年次大会 

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    Event date: 2017.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  9.  脳血管内皮細胞分化におけるNotch受容体O-GlcNAc修飾の役割 International conference

    平泉 光佑、澤口 翔伍、岡島 徹也

    2017年度生命科学系学会合同年次大会 

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    Event date: 2017.12

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  10. ガングリオシドGD3によるグリオーマの腫瘍微小環境の制御機構 Invited International conference

    Zhang P,Ohkawa Y, Momota H, Wakabayashi T, Ohmi Y, Bhuiyan RH, Furukawa Keiko,Okajima Tetsuya, Furukawa Koichi.

    2017年度生命科学系学会合同年次大会 

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    Event date: 2017.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  11. Mass Spectrometric analysis of O-GlcNAcylation on Notch EGF and function of N-Glycosylations on EGF domain-specific O-GlcNAc transferase (EOGT) International conference

    Sayad Md. Didarul Alam, Mitsutaka Ogawa, Hideyuki Takeuchi and Tetsuya Okajima

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    Event date: 2017.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  12. Requirement of O-fucosyltransferases for Developmental Processes International conference

    GlycoT 2006 

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    Event date: 2006.6

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  13. Chaperone activity of Protein O-fucosyltransferase I promotes Notch receptor folding. International conference

    HFSP 4th Awardees Annual Meeting 

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    Event date: 2005.6

    Language:English   Presentation type:Oral presentation (general)  

  14. Chaperone activity of Protein O-fucosyltransferase I within the endoplasmic reticulum promotes folding of the Notch receptor.

    Gordon Conference 

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    Event date: 2005.3

    Language:English   Presentation type:Oral presentation (invited, special)  

  15. Chaperone activity of Protein O-fucosyltransferase I promotes Notch receptor folding. International conference

    46th Annual Drosophila Research Conference 

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    Event date: 2005.3

    Language:English   Presentation type:Poster presentation  

  16. Chaperone activity of Protein O-fucosyltransferase I within the endoplasmic reticulum promotes folding of the Notch receptor. International conference

    GlycoT 2004 

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    Event date: 2004.11

    Language:English   Presentation type:Oral presentation (general)  

  17. Action of Protein O-fucosyltransferase 1 within the endoplasmic reticulum in maturation of the Notch receptor

    US/Japan Glyco 

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    Event date: 2004.11

    Language:English  

  18. Modulation of Notch-lingad binding by protein O-fucosyltransferase and fringe International conference

    HFSP 4th Awardees Annual Meeting 

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    Event date: 2004.5

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  19. Modulation of Notch-lingad binding by protein O-fucosyltransferase and fringe International conference

    45th Annual Drosophila Research Conference 

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    Event date: 2004.3

    Language:English   Presentation type:Poster presentation  

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Research Project for Joint Research, Competitive Funding, etc. 6

  1. Notch受容体糖鎖コードの時空間情報解読に向けたin vivoレポーターシステムの構築

    2018.10 - 2019.9

    自然科学研究助成 

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    Grant type:Competitive

  2. 糖転移酵素EOGTによるNotchシグナルと血管形成の制御機構の解明

    2018.4 - 2019.3

    研究助成 

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    Grant type:Competitive

  3. 糖転移酵素のよるNotch受容体の構造•機能の制御機構

    2007.4 - 2008.3

    武田科学振興財団 一般研究奨励 

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    Grant type:Competitive

  4. EGFドメイン特異的翻訳後修飾であるO-フコース/O-グルコース型糖鎖により制御を受ける新規シグナル関連タンパク質の探索

    2007.4 - 2008.3

  5. Control of Notch receptor structure and function by glycosyltransferases

    2006.6 - 2009.5

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    Grant type:Competitive

  6. EGFドメイン特異的糖転移酵素のよるNotch受容体の 構造•機能の調節機構

    2006.4 - 2007.3

    中島記念国際交流財団 日本人若手研究者研究助成金 

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    Grant type:Competitive

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KAKENHI (Grants-in-Aid for Scientific Research) 13

  1. 細胞外O-GlcNAc修飾のNotchシグナルと血管形成における役割

    2015.4 - 2017.3

    科学研究費補助金  基盤研究(B)

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    Authorship:Principal investigator 

  2. Notch シグナルとヘキソサミン経路を介した血液脳関門の制御

    2015.4 - 2017.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  3. 小胞体GlcNAc修飾の神経組織での役割

    2014.4 - 2016.3

    科学研究費補助金  新学術領域研究[公募研究]

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    Authorship:Principal investigator 

  4. モデル生物を活用した先天性脳疾患関連オーファン糖転移酵素の機能解明

    2013.4 - 2015.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  5. 神経組織の機能発現に関与する新規ドメイン特異糖鎖の解析

    2012.4 - 2014.3

    科学研究費補助金  新学術領域研究[公募研究]

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    Authorship:Principal investigator 

  6. 上皮成長因子様ドメインに特徴的な新規翻訳後修飾の同定と修飾機構の解析

    2009.4 - 2011.3

    科学研究費補助金  若手研究(B)

    岡島徹也

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    Authorship:Principal investigator 

    科学研究費補助金 若手研究(B) 403万円

  7. Ofut1によるNotch受容体の構造・機能の調節機構

    2006.4 - 2009.3

    科学研究費補助金  若手研究(A)

    岡島 徹也

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    Authorship:Principal investigator 

  8. 糖転移酵素群によるNOTCHタンパク質の分泌・分解の仕分け機構の解明

    Grant number:22H02815  2022.4 - 2025.3

    科学研究費助成事業  基盤研究(B)

    岡島 徹也, 近藤 裕史, 竹内 英之

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    Authorship:Principal investigator 

    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    NOTCHシグナルは細胞間相互作用の基本様式の1つであり、その活性化レベルが発生過程で適切に制御される。NOTCH受容体の活性化には、隣接した細胞間でリガンドと受容体が相互作用することが必要となるため、受容体の細胞膜への提示は精密に調節される必要がある。NOTCH受容体の分泌過程におけるO型糖鎖の重要性の理解が進んだ一方で、表裏一体と考えられる小胞体での分解の調節機構は不明である。本研究では、小胞体におけるNOTCH受容体の分解・分泌の仕分け機構への関与が示唆された新たな糖転移酵素に焦点をあて、その分子機構とその破綻により生じる病態の制御を目指す。
    (1) 糖転移酵素群によるNOTCHタンパク質の分泌・分解の仕分け機構の解析に向けて、主要な糖転移酵素であるPOFUT1、POGLUT1、EOGTを欠損したHEK293細胞を樹立した。予想通り、この3重変異細胞では、Notch1の細胞膜への発現が消失した。一方、POFUT1、POGLUT1、もしくはEOGTを発現させることにより、Notch1の細胞膜発現が部分的に回復した。従って、3重変異細胞はO型糖鎖の分泌過程における機能を反映することが確認できた。また、3重変異細胞では、O型糖鎖を完全に欠損するのか、一部、残留するO型糖鎖が存在するのかを確かめるために、内在性Notch受容体を免疫沈降により単離し、プロテアーゼ消化産物を質量分析をするための予備実験を実施した。
    (2) 3重変異細胞におけるNOTCH受容体の局在の異常を明らかにするために免疫染色をしたところ、NOTCH受容体の細胞内への蓄積が観察された。こうした異常NOTCH受容体の分解機構を明らかにするために、プロテアソームやオートファジーの阻害剤を用いて解析したが、異常NOTCH受容体の発現量は、これらの阻害剤により大きな変化は認められなかった。これらの結果より、3重変異細胞におけるNOTCH受容体の分解抵抗性の分子機構を明らかにすることが重要であると考えられた。
    (3) O型糖鎖欠損NOTCH受容体を認識し、分泌や分解に導く分子機構を明らかにするために、相互作用因子の探索を行った。1つは、BioID法を用いて糖鎖変異型NOTCH1と相互作用する分子を網羅的に同定した。別のアプローチとして、3重変異細胞に発現する内在性NOTCHに相互作用するタンパク質を免疫沈降法により同定した。複数の分子が両グループに共通しており、共通する分子に着目して、機能解析を進めることの有効性が示唆された。
    3重変異細胞におけるNOTCH受容体の分解抵抗性の分子機構に関する予備データが得られており、来年度以降、大きな研究の進展が期待できるため。
    (1) O型糖鎖欠損細胞の樹立と糖鎖解析
    3重変異細胞において、残留するO型糖鎖が存在するのかを確かめるために、内在性Notch受容体を免疫沈降により単離し、プロテアーゼ消化産物のOrbitrap Fusionを用いた質量分析を実施する。もし、残留するO型糖鎖が存在する場合は、野生型と3重変異細胞の間で、修飾率の差異が検出されるか検討をする。その結果、3重変異細胞におけるNotch受容体のフォールディングの状態を間接的に知ることができる。
    (2) O型糖鎖欠損によるNOTCH受容体の分解機構
    NOTCH受容体が蓄積する3重変異細胞において、各種化合物を用いたスクリーニングを行い、NOTCH受容体が分解される化合物を単離する。その化合物を用いることで、3重変異細胞におけるNOTCH受容体の分解抵抗性の分子機構を解明するための手がかりとする。
    (3) O型糖鎖欠損NOTCH受容体と相互作用する分子の同定と機能解析
    O型糖鎖欠損NOTCH受容体との相互作用因子に着目し、in vitroでの相互作用とその制御機構について明らかにする。

  9. 加齢に伴う運動能力低下におけるNotch1上の細胞外O-GlcNAc機能の解明

    Grant number:20F20410  2020.11 - 2023.3

    科学研究費助成事業  特別研究員奨励費

    岡島 徹也, LO PEIWEN

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    Authorship:Other 

    老化は、骨格筋のエネルギー産生の低下や筋肉量の減少を引き起こす。骨格筋では、1000以上のO-GlcNAc化タンパク質が同定されており、OGTによるPGC-1αのO-GlcNAc化はPGC-1αを安定化し、ミトコンドリア遺伝子の転写を促進することで筋萎縮を抑制し、エネルギー代謝を向上する。一方、骨格筋におけるEOGTによる細胞外O-GlcNAc化の役割は不明である。EOGTはNotch受容体をO-GlcNAc化することで、リガンド依存的なNOTCHシグナルを活性化することが知られている。本研究では、Notch1のO-GlcNAc修飾による筋運動能力の低下のメカニズムについて検証する。
    本研究では、当研究室で見出した細胞外O-GlcNAcの新規な役割を解析することを目的とした。これまでの研究で、内皮細胞におけるO-GlcNAcの役割が示唆されていた。EOGTは、小胞体におけるO-GlcNAc修飾を触媒する酵素である。この酵素は、上皮成長因子(EGF)様ドメインを特異的に修飾する。NOTCH受容体の細胞外領域は、主に多数のEGFドメインが繰り返した構造をとっている。Notch1の場合、36個のドメインのうち20個以上のEGFドメインがO-GlcNAcで修飾される可能性がある。したがって、NOTCHはO-GlcNAcで修飾される代表的な分子であり、生理的に重要なEOGTの基質となると考えられている。実際、EOGTの変異マウスは、NOTCHシグナル関連遺伝子のloss of function型変異を持つ動物に類似した表現型を示す。しかし、内皮細胞以外におけるEOGTの作用やNOTCH受容体との関連性は、まだ不明である。共同研究者のPeiwen Loは、Eogt欠損マウスとC2C12細胞のEogt変異体の表現型を解析することで、上記の問題を解決しようと取り組んだ。変異マウスにおける筋力の低下とC2C12細胞における筋分化の異常の分子基盤として、これまでに血管内皮細胞で解明されたNOTCH受容体を解するメカニズムとは異なる、PAMR1を含めた新たな基質候補タンパク質を介した分子機構が存在することが示唆された。
    令和4年度が最終年度であるため、記入しない。
    令和4年度が最終年度であるため、記入しない。

  10. Integrated analysis of atypical glycosylation as a basis for precise regulation of Notch signaling in the vascular endothelium

    Grant number:19H03416  2019.4 - 2022.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Okajima Tetsuya

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    Authorship:Principal investigator 

    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    To understand the molecular mechanism of precise regulation of NOTCH signaling via the O-GlcNAc transferase EOGT, this project clarified the basic mode of O-GlcNAc glycan structure that modifies NOTCH1 and developed a new analytical tool to clarify the dynamics of O-GlcNAc modification in vivo. We also succeeded in demonstrating the cooperative action of EOGT and other glycosyltransferases in the regulation of NOTCH signaling and the localization of EOGT expression in specific vascular endothelium and its involvement with vascular permeability.

  11. Regulation of Notch signaling in muscle satellite cells by O-glucose glycosylation

    Grant number:19H03176  2019.4 - 2022.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Takeuchi Hideyuki

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    Authorship:Coinvestigator(s) 

    We prviously found that abnormal O-glucose glycosylation of the Notch receptor causes a decrease in the number of satellite cells, the stem cells of muscle, and a decrease in Notch signaling in satellite cells, which leads to limb-girdle muscular dystrophy that develops in later adulthood [Cell 2008, EMBO Mol Med 2016]. This study suggests that, at least in HEK293T cells, xylosyl elongation of O-glucose glycans contributes to protein stability and quality control of Notch EGF repeats. Further studies are needed to elucidate the molecular mechanism of Notch receptor quality control by this type of glycosylation.

  12. Roles of Notch signaling and hexosamine pathway on regulation of blood brain barrier

    Grant number:15K15064  2015.4 - 2018.3

    OKAJIMA Tetsuya

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    Authorship:Principal investigator 

    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    Notch receptors are modified with unique post-translational modifications on epidermal growth (EGF)-like repeats. Previous studies elucidated the presence of O-GlcNAc modification and O-GlcNAc transferase, EOGT. O-GlcNAc modification by EOGT regulates DLL4-mediated Notch1 activation. In this study, we investigated roles of O-GlcNAc-mediated Notch regulation on integrity of blood vessels, which is pivotal for blood brain barrier. In Eogt-deficient mice, extravasation of biotin derivatives and deposition of fibrinogen were detected. Similar phenotype was observed in endothelial deletion of EOGT. In addition to N-cadherin, expression of components of tight junction were decreased, suggesting that EOGT-dependent Notch signaling represents a novel mechanism for regulation of blood vessels integrity.

  13. Roles of extracellular O-GlcNAc on Notch signaling and vascular development

    Grant number:26291020  2014.4 - 2018.3

    OKAJIMA Tetsuya

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    Authorship:Principal investigator 

    Grant amount:\16640000 ( Direct Cost: \12800000 、 Indirect Cost:\3840000 )

    Notch receptors are modified with unique post-translational modifications on epidermal growth (EGF)-like repeats at the extracellular domains. Previous studies revealed that besides O-fucose and O-glucose O-GlcNAc modification occurs on EGF repeats. However, biological function of O-GlcNAc on Notch receptors remained unknown. In this study, EOGT, a glycosyltransferase catalyzing O-GlcNAc modification of EGF domains, is inactivated in mice and phenotypical analyses were performed. Results revealed that specific EGF domains of Notch1 are modified with O-GlcNAc, which regulated DLL4-mediated Notch1 activation and thus Notch-dependent vascular development in the retina.

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Teaching Experience (On-campus) 6

  1. 生物の化学

    2015

  2. 生物学基礎I

    2015

  3. 大学院 基盤医科学実習

    2015

  4. 基礎医学セミナー

    2015

  5. 生化学実習

    2015

  6. 人体機能学

    2015

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