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Manipulation of G12/13 signaling and and drug development strategy

Research Project

Project/Area Number 21H04791
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionTohoku University

Principal Investigator

井上 飛鳥  東北大学, 薬学研究科, 教授 (50525813)

Co-Investigator(Kenkyū-buntansha) 加藤 英明  東京大学, 先端科学技術研究センター, 教授 (80805961)
Project Period (FY) 2021-04-05 – 2025-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥41,730,000 (Direct Cost: ¥32,100,000、Indirect Cost: ¥9,630,000)
Fiscal Year 2024: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2022: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2021: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
KeywordsGPCR / G12 / DREADD
Outline of Research at the Start

Gタンパク質共役型受容体(GPCR)は既存薬の約3割の作用標的となる重要な膜タンパク質である。このうち、G12とG13へとシグナル伝達を行うGPCRは解析が進んでおらずこれを標的とした薬は開発されていない。本研究では、G12やG13を自在にシグナルを誘導可能な人工GPCRを開発し、これを疾患モデルにマウスに発現させることで、G12シグナルやG13シグナルが疾患治療効果を有するかを明らかにする。

Outline of Annual Research Achievements

12共役型デザイナーGPCR(G12D)を肝細胞特異的に発現させたHep-G12Dマウスの体重抑制作用について、肝臓由来のホルモン(ヘパトカイン)に着目した解析を行った。その結果、ヘパトカインの1種であるFGF21がG12D活性化時に肝臓にて発現増加が見られることがわかった。さらに、抗FGF21抗体によりFGF21の機能阻害を行った条件において、高脂肪食負荷でのデザイナーリガンド投与によるHep-G12Dマウスの体重抑制作用が消失した。従って、肝臓のG12シグナルを介した体重抑制作用にFGF21が関与することを見出した。また、肝臓からのリポタンパク質分泌を測定したところ、デザイナーリガンドの慢性投与によりリポタンパク質分泌が増加することを見出した。脂肪G12共役型デザイナーGPCR発現マウスについて、寒冷刺激処置によるベージュ脂肪細胞の機能評価を行った。アドレナリンβ3受容体作動薬とデザイナーリガンドを投与した条件において、寒冷刺激処置による体温温度低下作用が減弱することを見出した。従って、脂肪細胞のG12シグナルは白色脂肪細胞のベージュ化を促進し、これが熱産生に機能であることがわかった。
G12DとGα12サブユニットの複合体およびG12DとGα13サブユニットの複合体の構造モデルを構築し分子動力学計算を行った。その結果、G12DとGαサブユニットの結合様式に差異が生じていることを見出した。Gα12とGα13の別々の相互作用に関与しうるG12Dの4カ所の残基について、アミノ酸置換のスクリーニングを行い、G13共役を強める4つの変異体を見出した。変異の組み合わせから、高いG13共役を示す二重変異体を作出した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

当初計画に沿って研究を実施し、計画通りの研究成果を得ることができた。本研究課題の主要業績となる論文掲載に至った(Ono et al., Sig Trans Target Ther 2023)。また、当初計画外の成果として、GPCRとGタンパク質の共役選択性の構造・動態基盤の解明(Ham et al., Commun Biol 2024; Jayakody et al., Sci Signal 2024)、GPCRとGタンパク質の共役選択性のインフォマティクス解析(Matic et al., Nat Commun 2023)、GPCRの構造解析(Park et al., Nat Commun 2023; Ishimoto et al., Nat Commun 2023; Kobayashi et al., Nature 2023)、新型コロナウイルス治療薬のオフターゲット標的同定(Ogawa et al., Commun Biol 2023)などの成果を得た。

Strategy for Future Research Activity

・G12共役型デザイナーGPCR(G12D)発現マウス解析
前年度までに、肝G12D発現マウスにおいて、代謝向上作用とこの効果を一部担うヘパトカインを同定した。本年度は、引き続き肝G12D発現マウスを解析し、デザイナーリガンド投与による肝G12シグナル誘導時の行動量への影響や糖代謝の変動を評価する。また、前年度の表皮G12D発現マウスの解析から見出した表皮の肥厚作用に着目し、本年度は皮膚バリア機能の変化を解析する。さらに、Bリンパ球特異的Cre発現マウスを導入し、G12DをB細胞に発現させたマウスを作出し、デザイナーリガンド投与による免疫応答について表現型解析を行う。

・G13共役型デザイナーGPCRの開発
前年度までの分子動力学計算と変異体スクリーニング実験から、G12Dに2つのアミノ酸置換を導入した改変GPCRにおいてG13共役活性の増強が生じた。本年度は、他のGタンパク質ファミリーのGタンパク質特異性を評価し、これらの非特異的なGタンパク質共役を低減する改変を試みる。また、前年度までにG12Dにおいて見出したGα12とGα13のC末端ヘリックスの差異が認識される機構が、他のG12/13共役型GPCRで保存されているかどうか、Gα12とGα13のC末端ヘリックスの1アミノ酸の相互置換変異体を用いて解析する。

Report

(4 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • 2021 Comments on the Screening Results   Annual Research Report
  • Research Products

    (75 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (11 results) Journal Article (52 results) (of which Int'l Joint Research: 39 results,  Peer Reviewed: 51 results,  Open Access: 28 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Remarks (3 results)

  • [Int'l Joint Research] Stanford University/UCSD/Indiana University(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Copenhagen University(デンマーク)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Tsinghua University(中国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Indian Institute of Technology(インド)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Stanford University/Thomas Jefferson University/Indiana University(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Chinese University of Hong Kong/Harbin Institute of Technology(中国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Indian Institute of Technology, Kanpur(インド)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Scuola Normale Superiore(イタリア)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Copenhagen(デンマーク)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Stanford University/UCSD(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Scuola Normale Superiore(イタリア)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq2024

    • Author(s)
      Ham Donghee、Inoue Asuka、Xu Jun、Du Yang、Chung Ka Young
    • Journal Title

      Communications Biology

      Volume: 7 Issue: 1 Pages: 362-362

    • DOI

      10.1038/s42003-024-06056-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of G protein-coupled receptor kinases in GLP-1R β-arrestin recruitment and internalisation2024

    • Author(s)
      McNeill Samantha M.、Lu Jessica、Marion C. Carino Carlo、Inoue Asuka、Zhao Peishen、Sexton Patrick M.、Wootten Denise
    • Journal Title

      Biochemical Pharmacology

      Volume: 222 Pages: 116119-116119

    • DOI

      10.1016/j.bcp.2024.116119

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development and basic performance verification of a rapid homogeneous bioassay for agonistic antibodies against the thyroid-stimulating hormone receptor2024

    • Author(s)
      Hoshina Motoki、Ojima Shiomi、Kawasaki Atsushi、Doi Kosuke、Ohta Satoshi、Inoue Asuka、Murayama Hiroshi
    • Journal Title

      Journal of Immunological Methods

      Volume: 528 Pages: 113655-113655

    • DOI

      10.1016/j.jim.2024.113655

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of biased agonism by Gαi/o-biased stapled peptide agonists of the relaxin-3 receptor2024

    • Author(s)
      Jayakody Tharindunee、Inoue Asuka、Kannan Srinivasaraghavan、Nakamura Gaku、Kawakami Kouki、Mendis Krishan、Nguyen Thanh-Binh、Li Jianguo、Herr Deron R.、Verma Chandra S.、Dawe Gavin S.
    • Journal Title

      Science Signaling

      Volume: 17 Issue: 823

    • DOI

      10.1126/scisignal.abl5880

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] GPCR signaling bias: an emerging framework for opioid drug development2024

    • Author(s)
      Kise Ryoji、Inoue Asuka
    • Journal Title

      The Journal of Biochemistry

      Volume: 175 Issue: 4 Pages: 367-376

    • DOI

      10.1093/jb/mvae013

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Structural and functional characterization of the endogenous agonist for orphan receptor GPR32024

    • Author(s)
      Chen Geng、Staffen Nico、Wu Zhangsong、Xu Xinyu、Pan Jinheng、Inoue Asuka、Shi Tingyi、Gmeiner Peter、Du Yang、Xu Jun
    • Journal Title

      Cell Research

      Volume: 34 Issue: 3 Pages: 262-265

    • DOI

      10.1038/s41422-023-00919-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Interaction modes of human orexin 2 receptor with selective and nonselective antagonists studied by NMR spectroscopy2024

    • Author(s)
      Imamura Kayo、Akagi Ken-Ichi、Miyanoiri Yohei、Tsujimoto Hirokazu、Hirokawa Takatsugu、Ashida Hideo、Murakami Kaori、Inoue Asuka、Suno Ryoji、Ikegami Takahisa、Sekiyama Naotaka、Iwata So、Kobayashi Takuya、Tochio Hidehito
    • Journal Title

      Structure

      Volume: 32 Issue: 3 Pages: 352-361

    • DOI

      10.1016/j.str.2023.12.008

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Basal interaction of the orphan receptor GPR101 with arrestins leads to constitutive internalization2024

    • Author(s)
      Abboud Dayana、Abboud Clauda、Inoue Asuka、Twizere Jean-Claude、Hanson Julien
    • Journal Title

      Biochemical Pharmacology

      Volume: 220 Pages: 116013-116013

    • DOI

      10.1016/j.bcp.2023.116013

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] GNAQ/GNA11 Mosaicism Causes Aberrant Calcium Signaling Susceptible to Targeted Therapeutics2024

    • Author(s)
      Zecchin Davide、Knopfel Nicole、Gluck Anna K.、Stevenson Mark、Sauvadet Aimie、Polubothu Satyamaanasa、Barberan-Martin Sara、Michailidis Fanourios、Bryant Dale、Inoue Asuka、Lines Kate E.、Hannan Fadil M.、Semple Robert K.、Thakker Rajesh V.、Kinsler Veronica A.
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 144 Issue: 4 Pages: 811-819.e4

    • DOI

      10.1016/j.jid.2023.08.028

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      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] G protein-biased LPAR1 agonism of prototypic antidepressants: Implication in the identification of novel therapeutic target for depression.2024

    • Author(s)
      Kajitani, N., Okada-Tsuchioka, M., Inoue, A., Miyano, K., Masuda, T., Boku, S., Iwamoto, K., Ohtsuki, S., Uezono, Y., Aoki, J., Takebayashi, M.
    • Journal Title

      Neuropsychopharmacology

      Volume: 49 Issue: 3 Pages: 561-572

    • DOI

      10.1038/s41386-023-01727-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of the real-time internalization of nine GPCRs reveals distinct dependence on arrestins and G proteins2024

    • Author(s)
      Moller Thor C.、Moo Ee Von、Inoue Asuka、Pedersen Mie F.、Brauner-Osborne Hans
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1871 Issue: 1 Pages: 119584-119584

    • DOI

      10.1016/j.bbamcr.2023.119584

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 22023

    • Author(s)
      Park Jae-Hyun、Kawakami Kouki、Ishimoto Naito、Ikuta Tatsuya、Ohki Mio、Ekimoto Toru、Ikeguchi Mitsunori、Lee Dong-Sun、Lee Young-Ho、Tame Jeremy R. H.、Inoue Asuka、Park Sam-Yong
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 7150-7150

    • DOI

      10.1038/s41467-023-42764-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gαs is dispensable for β-arrestin coupling but dictates GRK selectivity and is predominant for gene expression regulation by β2-adrenergic receptor2023

    • Author(s)
      Burghi Valeria、Paradis Justine S.、Officer Adam、Adame-Garcia Sendi Rafael、Wu Xingyu、Matthees Edda S.F.、Barsi-Rhyne Benjamin、Ramms Dana J.、Clubb Lauren、Acosta Monica、Tamayo Pablo、Bouvier Michel、Inoue Asuka、von Zastrow Mark、Hoffmann Carsten、Gutkind J. Silvio
    • Journal Title

      Journal of Biological Chemistry

      Volume: 299 Issue: 11 Pages: 105293-105293

    • DOI

      10.1016/j.jbc.2023.105293

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Eriodictyol and thymonin act as GPR35 agonists2023

    • Author(s)
      Nakashima Fumie、Qi Loh Wei、Wakabayashi Mayuka、Shimomura Sayako、Hattori Hiroyuki、Kita Masaki、Inoue Asuka、Uchida Koji、Shibata Takahiro
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 87 Issue: 12 Pages: 1514-1522

    • DOI

      10.1093/bbb/zbad125

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemogenetic activation of G12 signaling enhances adipose tissue browning2023

    • Author(s)
      Ono Y, Ito R, Arai K, Singh G, Saitoh T, Russell RB, Raimondi F, Aoki J, Sakai J, Inoue A.
    • Journal Title

      Signal Transduction and Targeted Therapy

      Volume: 8 Issue: 1 Pages: 307-307

    • DOI

      10.1038/s41392-023-01524-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system2023

    • Author(s)
      Sarma Parishmita、Carino Carlo Marion C.、Seetharama Deeksha、Pandey Shubhi、Dwivedi-Agnihotri Hemlata、Rui Xue、Cao Yubo、Kawakami Kouki、Kumari Poonam、Chen Yu-Chih、Luker Kathryn E.、Yadav Prem N.、Luker Gary D.、Laporte Stephane A.、Chen Xin、Inoue Asuka、Shukla Arun K.
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 4808-4808

    • DOI

      10.1038/s41467-023-40482-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] GPCRome-wide analysis of G-protein-coupling diversity using a computational biology approach2023

    • Author(s)
      Matic Marin、Miglionico Pasquale、Tatsumi Manae、Inoue Asuka、Raimondi Francesco
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 4361-4361

    • DOI

      10.1038/s41467-023-40045-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural basis of CXC chemokine receptor 1 ligand binding and activation2023

    • Author(s)
      Ishimoto Naito、Park Jae-Hyun、Kawakami Kouki、Tajiri Michiko、Mizutani Kenji、Akashi Satoko、Tame Jeremy R. H.、Inoue Asuka、Park Sam-Yong
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 4107-4107

    • DOI

      10.1038/s41467-023-39799-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Class B1 GPCR activation by an intracellular agonist2023

    • Author(s)
      Kobayashi Kazuhiro、Kawakami Kouki、Kusakizako Tsukasa、Tomita Atsuhiro、Nishimura Michihiro、Sawada Kazuhiro、Okamoto Hiroyuki H.、Hiratsuka Suzune、Nakamura Gaku、Kuwabara Riku、Noda Hiroshi、Muramatsu Hiroyasu、Shimizu Masaru、Taguchi Tomohiko、Inoue Asuka、Murata Takeshi、Nureki Osamu
    • Journal Title

      Nature

      Volume: 618 Issue: 7967 Pages: 1085-1093

    • DOI

      10.1038/s41586-023-06169-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural basis of omega-3 fatty acid receptor FFAR4 activation and G protein coupling selectivity2023

    • Author(s)
      Yin Han、Inoue Asuka、Ma Zhengxiong、Zhu Xinyan、Xia Ruixue、Xu Zhenmei、Wang Na、Duan Yaning、Zhang Anqi、Guo Changyou、He Yuanzheng
    • Journal Title

      Cell Research

      Volume: 33 Issue: 8 Pages: 644-647

    • DOI

      10.1038/s41422-023-00835-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Stabilization of pre-existing neurotensin receptor conformational states by β-arrestin-1 and the biased allosteric modulator ML3142023

    • Author(s)
      Bumbak Fabian、Bower James B.、Zemmer Skylar C.、Inoue Asuka、Pons Miquel、Paniagua Juan Carlos、Yan Fei、Ford James、Wu Hongwei、Robson Scott A.、Bathgate Ross A. D.、Scott Daniel J.、Gooley Paul R.、Ziarek Joshua J.
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 3328-3328

    • DOI

      10.1038/s41467-023-38894-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular mechanism of fatty acid activation of FFAR12023

    • Author(s)
      Kumari Punita、Inoue Asuka、Chapman Karen、Lian Peng、Rosenbaum Daniel M.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 22

    • DOI

      10.1073/pnas.2219569120

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction2023

    • Author(s)
      Ogawa Akiko、Ohira Seiya、Kato Yuri、Ikuta Tatsuya、Yanagida Shota、Mi Xinya、Ishii Yukina、Kanda Yasunari、Nishida Motohiro、Inoue Asuka、Wei Fan-Yan
    • Journal Title

      Communications Biology

      Volume: 6 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s42003-023-04888-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure-affinity and structure-residence time relationships of macrocyclic Gαq protein inhibitors2023

    • Author(s)
      Voss Jan H.、Crusemann Max、Bartling Christian R.O.、Kehraus Stefan、Inoue Asuka、Konig Gabriele M.、Stromgaard Kristian、Muller Christa E.
    • Journal Title

      iScience

      Volume: 26 Issue: 4 Pages: 106492-106492

    • DOI

      10.1016/j.isci.2023.106492

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Design and Synthesis of Orexin 1 Receptor-Selective Agonists2023

    • Author(s)
      Keita Iio, Kao Hashimoto, Yasuyuki Nagumo, Mao Amezawa, Taisei Hasegawa, Naoshi Yamamoto, Noriki Kutsumura, Katsuhiko Takeuchi, Yukiko Ishikawa, Hikari Yamamoto, Akihisa Tokuda, Tetsu Sato, Yasuo Uchida, Asuka Inoue, Ryuji Tanimura, Masashi Yanagisawa, Hiroshi Nagase, Tsuyoshi Saitoh
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 66 Issue: 8 Pages: 5453-5464

    • DOI

      10.1021/acs.jmedchem.2c01773

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Function and dynamics of the intrinsically disordered carboxyl terminus of β2 adrenergic receptor2023

    • Author(s)
      Heng Jie、Hu Yunfei、Perez-Hernandez Guillermo、Inoue Asuka、Zhao Jiawei、Ma Xiuyan、Sun Xiaoou、Kawakami Kouki、Ikuta Tatsuya、Ding Jienv、Yang Yujie、Zhang Lujia、Peng Sijia、Niu Xiaogang、Li Hongwei、Guixa-Gonzalez Ramon、Jin Changwen、Hildebrand Peter W.、Chen Chunlai、Kobilka Brian K.
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 2005-2005

    • DOI

      10.1038/s41467-023-37233-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization2023

    • Author(s)
      Kjaer Viktoria M.S.、Daugvilaite Viktorija、Stepniewski Tomasz M.、Madsen Christian M.、Jorgensen Astrid S.、Bhuskute Kaustubh R.、Inoue Asuka、Ulven Trond、Benned-Jensen Tau、Hjorth Siv A.、Hjorto Gertrud M.、Moo Ee Von、Selent Jana、Rosenkilde Mette M.
    • Journal Title

      Science Signaling

      Volume: 16 Issue: 779

    • DOI

      10.1126/scisignal.abl4283

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Phosphorylation barcodes direct biased chemokine signaling at CXCR32023

    • Author(s)
      Eiger Dylan S.、Smith Jeffrey S.、Shi Tujin、Stepniewski Tomasz Maciej、Tsai Chia-Feng、Honeycutt Christopher、Boldizsar Noelia、Gardner Julia、Nicora Carrie D.、Moghieb Ahmed M.、Kawakami Kouki、Choi Issac、Hicks Chloe、Zheng Kevin、Warman Anmol、et al.
    • Journal Title

      Cell Chemical Biology

      Volume: 30 Issue: 4 Pages: 362-382.e8

    • DOI

      10.1016/j.chembiol.2023.03.006

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Insights into distinct signaling profiles of the μOR activated by diverse agonists2023

    • Author(s)
      Qu Qianhui、Huang Weijiao、Aydin Deniz、Paggi Joseph M.、Seven Alpay B.、Wang Haoqing、Chakraborty Soumen、Che Tao、DiBerto Jeffrey F.、Robertson Michael J.、Inoue Asuka、Suomivuori Carl-Mikael、Roth Bryan L.、Majumdar Susruta、Dror Ron O.、Kobilka Brian K.、Skiniotis Georgios
    • Journal Title

      Nature Chemical Biology

      Volume: 19 Issue: 4 Pages: 423-430

    • DOI

      10.1038/s41589-022-01208-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ectodomain shedding of EGFR ligands serves as an activation readout for TRP channels2023

    • Author(s)
      Tatsumi Manae、Kishi Takayuki、Ishida Satoru、Kawana Hiroki、Uwamizu Akiharu、Ono Yuki、Kawakami Kouki、Aoki Junken、Inoue Asuka
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 1 Pages: e0280448-e0280448

    • DOI

      10.1371/journal.pone.0280448

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor2023

    • Author(s)
      Xu Jun、Wang Qinggong、Hubner Harald、Hu Yunfei、Niu Xiaogang、Wang Haoqing、Maeda Shoji、Inoue Asuka、Tao Yuyong、Gmeiner Peter、Du Yang、Jin Changwen、Kobilka Brian K.
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 376-376

    • DOI

      10.1038/s41467-022-35726-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of Gαi knock-out HEK293 cells illuminates Gαi-coupling diversity of GPCRs2023

    • Author(s)
      Ono Yuki、Kawakami Kouki、Nakamura Gaku、Ishida Satoru、Aoki Junken、Inoue Asuka
    • Journal Title

      Communications Biology

      Volume: 6 Issue: 1 Pages: 112-112

    • DOI

      10.1038/s42003-023-04465-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation2023

    • Author(s)
      Liang Jiale、Inoue Asuka、Ikuta Tatsuya、Xia Ruixue、Wang Na、Kawakami Kouki、Xu Zhenmei、Qian Yu、Zhu Xinyan、Zhang Anqi、Guo Changyou、Huang Zhiwei、He Yuanzheng
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 1012-1012

    • DOI

      10.1038/s41467-023-36575-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification and Functional Characterization of Fungal Chalcone Synthase and Chalcone Isomerase2023

    • Author(s)
      Furumura Sho、Ozaki Taro、Sugawara Akihiro、Morishita Yohei、Tsukada Kento、Ikuta Tatsuya、Inoue Asuka、Asai Teigo
    • Journal Title

      Journal of Natural Products

      Volume: 86 Issue: 2 Pages: 398-405

    • DOI

      10.1021/acs.jnatprod.2c01027

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phenotypic evaluation of constitutive GPCR/G-protein signaling in zebrafish embryos and larvae2022

    • Author(s)
      Shibata Takeaki、Kawakami Kouki、Kawana Hiroki、Aoki Junken、Inoue Asuka
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 602 Pages: 70-76

    • DOI

      10.1016/j.bbrc.2022.02.098

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Common coupling map advances GPCR-G protein selectivity2022

    • Author(s)
      Hauser Alexander S、Avet Charlotte、Normand Claire、Mancini Arturo、Inoue Asuka、Bouvier Michel、Gloriam David E
    • Journal Title

      eLife

      Volume: 11

    • DOI

      10.7554/elife.74107

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Activation and allosteric regulation of the orphan GPR88-Gi1 signaling complex2022

    • Author(s)
      Chen Geng、Xu Jun、Inoue Asuka、Schmidt Maximilian F.、Bai Chen、Lu Qiuyuan、Gmeiner Peter、Liu Zheng、Du Yang
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 2375-2375

    • DOI

      10.1038/s41467-022-30081-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cryo-EM structures of the β3 adrenergic receptor bound to solabegron and isoproterenol2022

    • Author(s)
      Nureki Ikko、Kobayashi Kazuhiro、Tanaka Tatsuki、Demura Kanae、Inoue Asuka、Shihoya Wataru、Nureki Osamu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 611 Pages: 158-164

    • DOI

      10.1016/j.bbrc.2022.04.065

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of Ligands and Transducers on the Neurotensin Receptor 1 Conformational Ensemble2022

    • Author(s)
      Dixon Austin D.、Inoue Asuka、Robson Scott A.、Culhane Kelly J.、Trinidad Jonathan C.、Sivaramakrishnan Sivaraj、Bumbak Fabian、Ziarek Joshua J.
    • Journal Title

      Journal of the American Chemical Society

      Volume: 144 Issue: 23 Pages: 10241-10250

    • DOI

      10.1021/jacs.2c00828

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] PRECOGx: exploring GPCR signaling mechanisms with deep protein representations2022

    • Author(s)
      Matic Marin、Singh Gurdeep、Carli Francesco、De Oliveira Rosa Natalia、Miglionico Pasquale、Magni Lorenzo、Gutkind J Silvio、Russell Robert B、Inoue Asuka、Raimondi Francesco
    • Journal Title

      Nucleic Acids Research

      Volume: 50 Issue: W1 Pages: W598-W610

    • DOI

      10.1093/nar/gkac426

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface2022

    • Author(s)
      Heo Yunseok、Ishimoto Naito、Jeon Ye-Eun、Yun Ji-Hye、Ohki Mio、Anraku Yuki、Sasaki Mina、Kita Shunsuke、Fukuhara Hideo、Ikuta Tatsuya、Kawakami Kouki、Inoue Asuka、Maenaka Katsumi、Tame Jeremy R. H.、Lee Weontae、Park Sam-Yong
    • Journal Title

      PLOS Biology

      Volume: 20 Issue: 8 Pages: e3001714-e3001714

    • DOI

      10.1371/journal.pbio.3001714

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endogenous ligand recognition and structural transition of a human PTH receptor2022

    • Author(s)
      Kobayashi Kazuhiro、Kawakami Kouki、Kusakizako Tsukasa、Miyauchi Hirotake、Tomita Atsuhiro、Kobayashi Kan、Shihoya Wataru、Yamashita Keitaro、Nishizawa Tomohiro、Kato Hideaki E.、Inoue Asuka、Nureki Osamu
    • Journal Title

      Molecular Cell

      Volume: 82 Issue: 18 Pages: 3468-3483

    • DOI

      10.1016/j.molcel.2022.07.003

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Allosteric modulation of GPCR-induced β-arrestin trafficking and signaling by a synthetic intrabody2022

    • Author(s)
      Baidya Mithu、Chaturvedi Madhu、Dwivedi-Agnihotri Hemlata、Ranjan Ashutosh、Devost Dominic、Namkung Yoon、Stepniewski Tomasz Maciej、Pandey Shubhi、Baruah Minakshi、Panigrahi Bhanupriya、Sarma Parishmita、Yadav Manish K.、Maharana Jagannath、Banerjee Ramanuj、Kawakami Kouki、Inoue Asuka、et al
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 4634-4634

    • DOI

      10.1038/s41467-022-32386-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural insights into the G protein selectivity revealed by the human EP3-Gi signaling complex2022

    • Author(s)
      Ryoji Suno, Yukihiko Sugita, Kazushi Morimoto, Hiroko Takazaki, Hirokazu Tsujimoto, Mika Hirose, Chiyo Suno-Ikeda, Norimichi Nomura, Tomoya Hino, Asuka Inoue, Kenji Iwasaki, Takayuki Kato, So Iwata, Takuya Kobayashi
    • Journal Title

      Cell Rep.

      Volume: 40(11) Issue: 11 Pages: 111323-111323

    • DOI

      10.1016/j.celrep.2022.111323

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhanced membrane binding of oncogenic G protein αqQ209L confers resistance to inhibitor YM-2548902022

    • Author(s)
      Randolph Clinita E.、Dwyer Morgan B.、Aumiller Jenna L.、Dixon Alethia J.、Inoue Asuka、Osei-Owusu Patrick、Wedegaertner Philip B.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 11 Pages: 102538-102538

    • DOI

      10.1016/j.jbc.2022.102538

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Membrane phosphoinositides regulate GPCR-β-arrestin complex assembly and dynamics2022

    • Author(s)
      Janetzko John、Kise Ryoji、Barsi-Rhyne Benjamin、Siepe Dirk H.、Heydenreich Franziska M.、Kawakami Kouki、Masureel Matthieu、Maeda Shoji、Garcia K. Christopher、von Zastrow Mark、Inoue Asuka、Kobilka Brian K.
    • Journal Title

      Cell

      Volume: 185 Issue: 24 Pages: 4560-4573

    • DOI

      10.1016/j.cell.2022.10.018

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synthesis of unnatural morphinan compounds to induce itch-like behaviors in mice: Towards the development of MRGPRX2 selective ligands2022

    • Author(s)
      Iio Keita、Kutsumura Noriki、Nagumo Yasuyuki、Saitoh Tsuyoshi、Tokuda Akihisa、Hashimoto Kao、Yamamoto Naoshi、Kise Ryoji、Inoue Asuka、Mizoguchi Hirokazu、Nagase Hiroshi
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 56 Pages: 128485-128485

    • DOI

      10.1016/j.bmcl.2021.128485

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterotrimeric Gq proteins?act as a switch for GRK5/6 selectivity underlying β-arrestin transducer bias2022

    • Author(s)
      Kawakami Kouki、Yanagawa Masataka、Hiratsuka Suzune、Yoshida Misaki、Ono Yuki、Hiroshima Michio、Ueda Masahiro、Aoki Junken、Sako Yasushi、Inoue Asuka
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 870-870

    • DOI

      10.1038/s41467-022-28056-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biased agonists of the chemokine receptor CXCR3 differentially signal through Gα <sub>i</sub> :β-arrestin complexes2022

    • Author(s)
      Zheng Kevin、Smith Jeffrey S.、Eiger Dylan S.、Warman Anmol、Choi Issac、Honeycutt Christopher C.、Boldizsar Noelia、Gundry Jaimee N.、Pack Thomas F.、Inoue Asuka、Caron Marc G.、Rajagopal Sudarshan
    • Journal Title

      Science Signaling

      Volume: 15 Issue: 726

    • DOI

      10.1126/scisignal.abg5203

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors2021

    • Author(s)
      Pandey Shubhi、Kumari Punita、Baidya Mithu、Kise Ryoji、Cao Yubo、Dwivedi-Agnihotri Hemlata、Banerjee Ramanuj、Li Xaria X.、Cui Cedric S.、Lee John D.、Kawakami Kouki、Maharana Jagannath、Ranjan Ashutosh、Chaturvedi Madhu、Jhingan Gagan Deep、Laporte St?phane A.、Woodruff Trent M.、Inoue Asuka、Shukla Arun K.
    • Journal Title

      Molecular Cell

      Volume: 81 Issue: 22 Pages: 4605-4621.e11

    • DOI

      10.1016/j.molcel.2021.09.007

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Label-Free Investigations on the G Protein Dependent Signaling Pathways of Histamine Receptors2021

    • Author(s)
      Seibel-Ehlert Ulla、Plank Nicole、Inoue Asuka、Bernhardt Guenther、Strasser Andrea
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 18 Pages: 9739-9739

    • DOI

      10.3390/ijms22189739

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structural basis of sphingosine-1-phosphate receptor 1 activation and biased agonism2021

    • Author(s)
      Xu Zhenmei、Ikuta Tatsuya、Kawakami Kouki、Kise Ryoji、Qian Yu、Xia Ruixue、Sun Ming-Xia、Zhang Anqi、Guo Changyou、Cai Xue-Hui、Huang Zhiwei、Inoue Asuka、He Yuanzheng
    • Journal Title

      Nature Chemical Biology

      Volume: 18 Issue: 3 Pages: 281-288

    • DOI

      10.1038/s41589-021-00930-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 化学遺伝学的手法を用いた脂肪肝におけるG12共役型GPCRの機能解析2023

    • Author(s)
      荒井魁斗、小野雄基、井上飛鳥
    • Organizer
      第22回次世代を担う若手のためのファーマ・バイオフォーラム2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] ケモジェネティクスを用いたG12シグナルの脂肪肝抑制効果とその機構解析2023

    • Author(s)
      荒井魁斗、小野雄基、井上飛鳥
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 結合様式の違いによる beta アレスチンの機能的、構造的差異2022

    • Author(s)
      桑原 莉来、川上 耕季、井上 飛鳥
    • Organizer
      日本生化学会東北支部第88回例会
    • Related Report
      2022 Annual Research Report
  • [Presentation] G12共役型DREADDを用いたG12シグナルの脂肪肝抑制作用の評価とその機構解析2022

    • Author(s)
      荒井魁斗、小野雄基、井上飛鳥
    • Organizer
      第17回 GPCR研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] デザイナーGPCRを用いたG12シグナルの表皮における機能解析2022

    • Author(s)
      平井夏実、古川史歩、小野雄基、井上飛鳥
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Biased ligands and GRK-subtype selectivity: negative regulations of GRK5/6 by Gq and its consequence for β-arrestin functionality2021

    • Author(s)
      Asuka Inoue
    • Organizer
      TARGET 2035-Chemical Probes for GPCRs
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] GPCR effector-KO HEK293 cell lines - how to dissect complexity of GPCR signaling2021

    • Author(s)
      Asuka Inoue
    • Organizer
      British Pharmacological Society Pharmacology 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Back and forth between purified and cellular systems for GPCR biology2021

    • Author(s)
      井上飛鳥
    • Organizer
      第59回日本生物物理学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 酸化ストレス代謝物の標的膜受容体とその活性化検出2021

    • Author(s)
      井上飛鳥
    • Organizer
      第74回日本酸化ストレス学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Remarks] 研究室HP

    • URL

      http://www.pharm.tohoku.ac.jp/~seika/2020/index.html

    • Related Report
      2023 Annual Research Report 2021 Annual Research Report
  • [Remarks] 東北大学薬学研究科HP

    • URL

      http://www.pharm.tohoku.ac.jp/home/information/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 東北大学分子細胞生化学分野ホームページ

    • URL

      http://www.pharm.tohoku.ac.jp/~seika/2020/index.html

    • Related Report
      2022 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2024-12-25  

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