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Fundamental research for quantitative control of the surface GPCRs

Research Project

Project/Area Number 23590067
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAMURA Motonao  東京大学, 医学(系)研究科(研究院), 准教授 (40431762)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsG蛋白質共役型受容体 / 品質管理 / 細胞内輸送 / 翻訳後修飾 / リン酸化 / ユビキチン化 / 糖鎖修飾 / Gタンパク質共役型受容体
Research Abstract

In this program, we have obtained several useful results required for the quantitative control of surface GPCRs. (1) GPCRs lacking N-glyco-modification (e.g., alpha-2B adrenergic receptor) also receive the quality control by ERAD system in the ER, resulting in the regulation for the surface trafficking of the receptor. (2) We confirmed the conjugation of mono-ubiquitin (mono-Ub) to the lysine residue in the C-terminus of leukotriene B4 type-I receptor (BLT1). Moreover, we identified the candidate Ub-ligase by the Ub-split yeast two-hybrid system using the full length of BLT1 as a bait (unpublished). (3) We determined the basal and ligand (LTB4)-induced phosphorylation sites in BLT1. The biological significance of both modifications (mono-ubiquitination and phosphorylation) in the intracellular trafficking of BLT1 is under investigation in our group using mutant BLT1s lacking these modifications.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (34 results)

All 2014 2013 2012 2011

All Journal Article (16 results) (of which Peer Reviewed: 9 results) Presentation (18 results)

  • [Journal Article] Pathogenic role of CXCR2/BLT1-driven neutrophil infiltration for induction of psoriatic skin inflammation2014

    • Author(s)
      Sumida,H., Yanagida,K., Kita,Y., Abe,J., Matsushima,K., Nakamura,M., Ishii,S., Sato,S., and Shimizu,T.
    • Journal Title

      J.Immunol

      Volume: (in press)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Pathogenic role of CXCR2/BLT1-driven neutrophil infiltration for induction of psoriatic skin inflammation.2014

    • Author(s)
      Sumida,H., Yanagida,K., Kita,Y., Abe,J., Matsushima,K., Nakamura,M., Ishii,S., Sato,S., and Shimizu,T.
    • Journal Title

      J.Immunol

      Volume: 掲載確定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PLA2G3, a mammalian homolog of anaphylactic phospholipase A2 in bee venom, facilitates proper maturation of mast cells through the paracrine PGD2 loop2013

    • Author(s)
      Taketomi,Y., Ueno,N., Kojima,T., Kawana,M., Tanaka,S., Sakanaka,M., Nakamura,M., Sato,H., Nishito,Y., Kambe,N., Yamamoto,K., Gelb,M.H., Arita,M., Yokomizo,T.,Watanabe,K,.Nakamura,M., Shimizu,T., Hirai,H., Aritake,K., Urade,Y., Morimoto,K., Sugimoto,Y., Narumiya,S., Hara,S., and Murakami,M.
    • Journal Title

      Nature immunology

      Volume: 14 Pages: 554-566

    • Related Report
      2013 Final Research Report
  • [Journal Article] Discovery of INT131: a selective PPARmodulator that enhances insulin sensitivity2013

    • Author(s)
      Taygerly,J.P., McGee,L.R., Rubenstein,S.M., Houze,J.B., Cushing,T.D., Li,Y., Motani,A., Chen,J-L., Frankmoelle,W., Ye,G., Learned,M.R., Jaen,J., Miao,S., Timmermans,P.B., Thoolen,M., Kearney,P., Flygare,J., Beckmann,H., Weiszmann,J., Lindstrom,M., Walker,N., Liu,J., Biermann,D., Wang,Z., Hagiwara,A., Iida,T., Aramaki,H., Kitao,Y., Shinkai,H., Furukawa,N., Nishiu,J., and Nakamura,M.
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 21 Pages: 979-992

    • Related Report
      2013 Final Research Report
  • [Journal Article] Amino acid residues of G-protein coupled receptors critical for endoplasmic reticulum export and trafficking2013

    • Author(s)
      Nakamura,M., Yasuda,D., Hirota,N., Yamamoto,T., Yamaguchi,S., Shimizu,T., and Nagamune,T.
    • Journal Title

      Methods in Enzymol

      Volume: 521 Pages: 203-216

    • Related Report
      2013 Final Research Report
  • [Journal Article] 特異的リガンドによる小胞体蓄積GPCRの細胞膜への搬出2013

    • Author(s)
      安田大恭、中村元直
    • Journal Title

      生化学

      Volume: 85

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] Discovery of INT131: a selective PPARγ modulator that enhances insulin sensitivity.2013

    • Author(s)
      Taygerly,J.P., McGee,L.R., Cushing,T.D., Li,Y., Motani,A., Chen,J-L., Frankmoelle,W., Ye,G., Learned,M.R., Jaen,J., Miao,S., Timmermans,P.B., Thoolen,M., Kearney,P., Flygare,J., Beckmann,H., Weiszmann,J., Lindstrom,M., Walker,N., Liu,J., Biermann,D., Wang,Z., Nishiu,J., and Nakamura,M
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 21 Pages: 979-992

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mast cell maturation is driven via a novel group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis.2013

    • Author(s)
      Taketomi, Y., Morimoto, K., Murakami, M., et al., 他30名
    • Journal Title

      Nature Immunol.

      Volume: (印刷中) Issue: 6 Pages: 554-63

    • DOI

      10.1038/ni.2586

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amino acid residues of G-protein coupled receptors critical for endoplasmic reticulum export and trafficking2013

    • Author(s)
      Nakamura,M., Yasuda,D., Hirota,N., Yamamoto,T., Yamaguchi,S., Shimizu,T., and Nagamune,T
    • Journal Title

      Methods in Enzymol.

      Volume: 521 Pages: 203-216

    • DOI

      10.1016/b978-0-12-391862-8.00011-9

    • ISBN
      9780123918628
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Discovery of INT131: a selective PPARγ modulator that enhances insulin sensitivity.2013

    • Author(s)
      Taygerly,J.P., Nishiu,J., and Nakamura,M.
    • Journal Title

      Bioorganic & Medicinal Chemistry.

      Volume: 掲載確定

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] PLA2G3, a mammalian homolog of anaphylactic phospholipase A2 in bee venom, facilitates proper maturation of mast cells through the paracrine PGD2 loop.2013

    • Author(s)
      Taketomi,Y., Sakanaka,M.,Nakamura,M., Shimizu,T., Hara,S., and Murakami,M
    • Journal Title

      Nature immunology

      Volume: 掲載確定

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage2012

    • Author(s)
      Echigo,R., Shimohata,N., Karatsu,K., Yano,F., Kayasuga-Kariya,Y., Fujisawa,A., Ohto,T., Kita,Y., Nakamura,M., Suzuki,S., Mochizuki,M., Shimizu,T., Chung,U-i., and Nobuo Sasaki,N.
    • Journal Title

      J. Translational Medicine

      Volume: Apr 30

    • Related Report
      2013 Final Research Report
  • [Journal Article] Identification and characterization of a novel chemotype MEK inhibitor able to alter the phosphorylation state of MEK1/22012

    • Author(s)
      Yoshida,T., Kakegawa,J., Yamaguchi,T., Hantani,Y., Okajima,N., Sakai,T., Watanabe,Y., and Nakamura,M.
    • Journal Title

      Oncotarget

      Volume: 3 Pages: 1533-1545

    • Related Report
      2013 Final Research Report
  • [Journal Article] Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage2012

    • Author(s)
      Echigo R, Shimohata N, Karatsu K, Yano F, Kayasuga-Kariya Y, Fujisawa A, Ohto T, Kita Y, Nakamura M, Suzuki S, Mochizuki M, Shimizu T, Chung UI, Sasaki N
    • Journal Title

      J Transl Med

      Volume: 10 Issue: 1 Pages: 80-80

    • DOI

      10.1186/1479-5876-10-80

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of a novel chemotype MEK inhibitor able to alter the phosphorylation state of MEK1/2.2012

    • Author(s)
      Yoshida,T., Kakegawa,J., Yamaguchi,T., Hantani,Y., Okajima,N., Sakai,T., Watanabe,Y., and Nakamura,M.
    • Journal Title

      Oncotarget

      Volume: 3 Pages: 1533-1545

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amino acid residues of G-protein coupled receptors critical for endoplasmic reticulum export and trafficking.2012

    • Author(s)
      Nakamura,M., Yasuda,D., Hirota,N., Yamamoto,T., Yamaguchi,S., Shimizu,T., and Nagamune,T.
    • Journal Title

      Methods in Enzymology

      Volume: (掲載確定)

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Analysis of human leukotriene B4 type 1 receptor phosphorylation sites by Phos-tag SDS-PAGE"Bioactive Lipids in Cancer, Inflammation, and Related Diseases2013

    • Author(s)
      Yoshimitsu Nakanishi, Keisuke Yanagida, Takao Shimizu, and Motonao Nakamura
    • Organizer
      13th International Conference
    • Place of Presentation
      San Juan, Puerto Rico
    • Year and Date
      2013-11-04
    • Related Report
      2013 Final Research Report
  • [Presentation] 膜リン脂質代謝と脂質メディエーター受容体の新展開2013

    • Author(s)
      中村元直、清水孝雄
    • Organizer
      2012年度日本農芸化学会大会、シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2013-03-25
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of amino acid residues responsible for basal and ligand-induced phosphorylations of human leukotriene B4 type 1 receptor by Phos-tag SDS-PAGE2013

    • Author(s)
      Yoshimitsu Nakanishi, Keisuke Yanagida, Takao Shimizu, and Motonao Nakamura
    • Organizer
      Bioactive Lipids in Cancer, Inflammation, and Related Diseases
    • Place of Presentation
      San Juan, Puerto Rico
    • Related Report
      2013 Annual Research Report
  • [Presentation] ニコチン酸受容体GPR109Aが有するN型糖鎖付加のための非sequon配列の重要性について2012

    • Author(s)
      安田大恭、井村裕己、石井聡、清水孝雄、中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      福岡(国際会議場)
    • Related Report
      2013 Final Research Report
  • [Presentation] Phos-tag SDS-PAGE法を用いたロイコトリエンB4第一受容体(BLT1)におけるリン酸化部位の解析2012

    • Author(s)
      中西由光、清水孝雄、中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      福岡(国際会議場)
    • Related Report
      2013 Final Research Report
  • [Presentation] N型糖鎖がないα2Bアドレナリン受容体の小胞体内品質管理について2012

    • Author(s)
      歌代奈和、井村裕己、安田大恭、石浦章一、清水孝雄、中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      福岡(国際会議場)
    • Related Report
      2013 Final Research Report
  • [Presentation] N型糖鎖修飾がないα2Bアドレナリン受容体の小胞体内品質管理について2012

    • Author(s)
      歌代奈和、井村祐己、安田大恭、石浦章一、清水孝雄、中村元直
    • Organizer
      第85回日本生化学会年会
    • Place of Presentation
      福岡国際会議場 福岡県
    • Related Report
      2012 Research-status Report
  • [Presentation] Phos-tag SDS-PAGE法を用いたロイコトリエンB4第一受容体(BLT1)におけるリン酸化部位の解析2012

    • Author(s)
      中西由光、清水孝雄、中村元直
    • Organizer
      第85回日本生化学会年会
    • Place of Presentation
      福岡国際会議場 福岡県
    • Related Report
      2012 Research-status Report
  • [Presentation] ニコチン酸受容体GPR109aが有するN型糖鎖付加のための非sequon配列の重要性について2012

    • Author(s)
      安田大恭、井村祐己、石井聡、清水孝雄、中村元直
    • Organizer
      第85回日本生化学会年会
    • Place of Presentation
      福岡国際会議場 福岡県
    • Related Report
      2012 Research-status Report
  • [Presentation] 膜リン脂質代謝と脂質メディエーター受容体の新展開2012

    • Author(s)
      中村元直、清水孝雄
    • Organizer
      日本農芸化学会シンポジウム(招待講演)
    • Place of Presentation
      京都女子大(京都府)
    • Related Report
      2011 Research-status Report
  • [Presentation] ロイコトリエンB4第一受容体の遺伝子発現調節機構の解明2011

    • Author(s)
      吉田(橋立)智美、清水孝雄、中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      京都(国際会議場)
    • Related Report
      2013 Final Research Report
  • [Presentation] 結晶化のためのロイコトリエンB4受容体(BLT1)の熱安定性と抗BLT1モノクローナル抗体の作製2011

    • Author(s)
      堀哲也、菅原光明、中村元直,横溝岳彦,清水孝雄、宮野雅司
    • Organizer
      日本生化学会年会
    • Place of Presentation
      京都(国際会議場)
    • Related Report
      2013 Final Research Report
  • [Presentation] G蛋白質共役型受容体ファミリーにおけるN型糖鎖修飾の小胞体搬出に及ぼす影響2011

    • Author(s)
      井村祐己、清水孝雄,中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      京都(国際会議場)
    • Related Report
      2013 Final Research Report
  • [Presentation] 短鎖脂肪酸を認識するG蛋白質共役型受容体の血球内での発現制御に関する解析2011

    • Author(s)
      宮崎陽造、吉田(橋立)智美、清水孝雄、中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      京都(国際会議場)
    • Related Report
      2013 Final Research Report
  • [Presentation] ロイコトリエンB4第一受容体の遺伝子発現調節機構の解明2011

    • Author(s)
      吉田(橋立)智美、清水孝雄、中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      京都国際会議場(京都府)
    • Related Report
      2011 Research-status Report
  • [Presentation] 結晶化のためのロイコトリエンB4受容体(BLT1)の熱安定性と抗BLT1モノクローナル抗体の作製2011

    • Author(s)
      堀哲也、菅原光明、中村元直,横溝岳彦,清水孝雄、宮野雅司
    • Organizer
      日本生化学会年会
    • Place of Presentation
      京都国際会議場(京都府)
    • Related Report
      2011 Research-status Report
  • [Presentation] G蛋白質共役型受容体ファミリーにおけるN型糖鎖修飾の小胞体搬出に及ぼす影響2011

    • Author(s)
      井村祐己、清水孝雄,中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      京都国際会議場(京都府)
    • Related Report
      2011 Research-status Report
  • [Presentation] 短鎖脂肪酸を認識するG蛋白質共役型受容体の血球内での発現制御に関する解析2011

    • Author(s)
      宮崎陽造、吉田(橋立)智美、清水孝雄、中村元直
    • Organizer
      日本生化学会年会
    • Place of Presentation
      京都国際会議場(京都府)
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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