Autonomatous activation of GPCRs and inverse agonists

• Project/Area Number: 19591073
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokyo
• Principal Investigator: MAKITA Noriko The University of Tokyo, 医学部附属病院, 助教 (60353455)
• Co-Investigator(Kenkyū-buntansha): IIRI Taroh 東京大学, 医学部附属病院, 特任講師 (90313022)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: レセプター / G蛋白質 / 活性化 / インバースアゴニスト / 局在 / Gタンパク質 / 受容体 / 分子機構 / 疾患 / Gタンパク質病 / 機能選択性 / G蛋白質病

Research Abstract

We have investigated the mechanisms of agonist-independent autonomous activation of G-protein-coupled receptors, which is known to play important roles in disease mechanisms, and its regulation by inverse agonists, gene expression of mutant signaling molecules targeting receptor-G protein interaction, functionally selective regulation of receptors based on changes in localization of signaling molecules in cells.

Research Products

• [Journal Article] Sunitinib Induces Hypothyroidism with a Markedly Reduced Vascularity (2010)
  • Author(s): Makita N, Miyakawa M, Fujita T, Iiri T.
  • Journal Title: Thyroid 20 Pages: 323-326
  • Peer Reviewed
• [Journal Article] Sunitinib induces hypothyroidism with a markedly reduced vasculartiy. (2010)
  • Author(s): 槙田紀子, 他
  • Journal Title: Thyroid 20 Pages: 323-326
  • Peer Reviewed
• [Journal Article] Functionally Selective Activation in Ca-Sensing Receptors (2009)
  • Author(s): Makita N, Iiri T.
  • Journal Title: J.Pharmacol.Sci. 109 Pages: 37-37
• [Journal Article] Ca感知受容体の機能選択的活性化 : まれな疾患からのヒント (2009)
  • Author(s): 飯利太朗, 槙田紀子
  • Journal Title: 日本薬理学会雑誌 134 Pages: 244-247
  • NAID: 10025741842
• [Journal Article] Lack of Evidence for AT1R/B2R Heterodimerization in COS-7, HEK293, and NIH3T3 Cells-How Common is the AT1R/B2R Heterodimer? (2009)
  • Author(s): Hansen JL, Hansen JT, Speerchneider T, Lyngso C, Erikstrup N, Burstein ES, Weiner DM, Walther T, Makita N, Iiri T, Merten N, Kosteins E, Sheikh SP.
  • Journal Title: J.Biol.Chem. 284 Pages: 1831-1839
  • Peer Reviewed
• [Journal Article] Lack of evidence for AT1R/B2R heterodimerization-How common is the AT1R/B2R heterodimer? (2009)
  • Author(s): Hansen J, et al.
  • Journal Title: J.Biol.Chem 284 Pages: 1831-1839
  • Peer Reviewed
• [Journal Article] Ca感知受容体の機能選択的活性化:まれな疾患からのヒント (2009)
  • Author(s): 飯利太朗, 槙田紀子
  • Journal Title: 日本薬理学雑誌 134 Pages: 244-247
  • NAID: 10025741842
• [Journal Article] Lack of evidence for AT1R/B2R heterodimerization-How common is the AT1R/B2R hete. (2009)
  • Author(s): Hansen JL et al.
  • Journal Title: J. Biol. Chem 284 Pages: 1831-1839
  • Peer Reviewed
• [Journal Article] Calcium-sensing receptor (2008)
  • Author(s): Makita T, Iiri T.
  • Journal Title: AfCS Nature. Molecule Pages
  • Peer Reviewed
• [Journal Article] Calcium-sensing receptor (2008)
  • Author(s): Makita N and Iiri T
  • Journal Title: AfCS Nature (online)
  • Peer Reviewed
• [Journal Article] Calcium-sensing receptor (2008)
  • Author(s): Makita N and liri T
  • Journal Title: AfCS Nature online(掲載確定)
  • Peer Reviewed
• [Journal Article] Human Gsa Mutant Causes Pseudohypoparathyroidism Type1a/Neonatal Diarrhea, a Potential Cell-Specific Role of the Palmitoylation Cycle (2007)
  • Author(s): Makita N, Sato J, Rondard P, Fukamachi H, Yasuda Y, Aldred MA, Hashimoto M, Fujita T, Iiri T.
  • Journal Title: Proc.Natl.Acad.Sci.USA 104 Pages: 17424-17429
  • Peer Reviewed
• [Journal Article] An Acquired Hypocalciuric Hypercalcemia Autoantibody Induces Allosteric Transition among Active Human Ca-sensing Receptor Conformations (2007)
  • Author(s): Makita N, Sato J, Manaka K, Shoji Y, Oishi A, Hashimoto M, Fujita T, Iiri T.
  • Journal Title: Proc.Natl.Acad.Sci.USA 104 Pages: 5443-5448
  • Peer Reviewed
• [Journal Article] Acquired hypocalciuric hypercalcemia autoantibody induces allosteric transition amond multiple active condformations. (2007)
  • Author(s): Makita N, Iiri T, et. al.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A 104 Pages: 5443-5448
  • Peer Reviewed
• [Journal Article] Human Gsa mutant causes pseudohypoparathyroidism type Ia/neonatal diarrhea, a potential cell-specofic role of the palmitoylation cycle (2007)
  • Author(s): Makita N, Iiri T, et. al.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A 104 Pages: 17424-17429
  • Peer Reviewed
• [Presentation] Analysis of vasopressin V2 receptor mutants in partial nephrogenic diabetes insi〓 (2010)
  • Author(s): Makita N, et al.
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: 京都
  • Year and Date: 2010-03-26
• [Presentation] Analysis of Vasopressin V2 Receptor Mutants in Partial Nephrogenic Diabetes Insipidus and their Functional Rescue by Pharmacologic Chaperones (2010)
  • Author(s): Makita N, Manaka K, Takahashi K, Sato J, Oishi A, Yajima Y, Hashimoto M, Sekine K, Igarashi T, Fujita T, Iiri T.
  • Organizer: 14^<th> International Congress of Endocrinology
  • Place of Presentation: Kyoto
• [Presentation] Functionally Selective Activation in Calcium Sensing Receptor : a hint from a rare disease (2009)
  • Author(s): Taroh Iiri, Noriko Makita, Junichiro Sato
  • Organizer: 第82回日本薬理学会年次総会 シンポジウム Invited talk
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-18
• [Presentation] Sunitinib による甲状腺機能異常 (2009)
  • Author(s): 槙田紀子, 宮川めぐみ, 藤田恵, 和泉梢, 松井, 藤田敏郎, 飯利太朗
  • Organizer: 第52回日本甲状腺学会
  • Place of Presentation: 名古屋
• [Presentation] 部分尿崩症患者におけるV2受容体変異とG蛋白質相互作用の解析 (2009)
  • Author(s): 高橋和浩, 関根孝司, 久野正貴, 飯田厚子, 秋岡祐子, 三浦健一郎, 田久保憲行, 間中勝則, 槙田紀子, 飯利太朗, 藤田敏郎, 五十嵐隆
  • Organizer: 第52回日本腎臓学会学術総会
• [Presentation] Fuctionlly selective ativation of GPCR:a hint from a rare disease (2008)
  • Author(s): Taroh Iiri and Noriko Makita
  • Organizer: Keystone Symposia: Gproteim-coupled receptor(Invited Talk)
  • Place of Presentation: killarney, Ireland
  • Year and Date: 2008-05-19
• [Presentation] Biased Agonism in class C GPCRs : a hint from a rare disease (2008)
  • Author(s): Noriko Makita, Taroh Iiri
  • Organizer: 7^<th> International Meeting on Metabotropic Glutamate Receptors
  • Place of Presentation: Invited talk. Taormina, Italy
• [Presentation] Functionally Selective Activation of a GPCR : a Hint from a Rare Disese (2008)
  • Author(s): Taroh Iiri, Noriko Makita
  • Organizer: Keystone Symposia. G protein coupled receptors:New insights infunctional regulation and clinical application
  • Place of Presentation: Invited talk. Ireland
• [Presentation] Atypical PHP-Iaで発見された新規Gsα変異体の解析 (2008)
  • Author(s): 槙田紀子, 佐藤純一郎, 間中勝則, 矢嶋由紀, 大石篤郎, 橋本真紀子, 藤田敏郎, 飯利太朗
  • Organizer: 第81回日本内分泌学会
  • Place of Presentation: 青森
• [Presentation] Atypical PHP-Iaで発見された新規Gsα変異体の解析 (2008)
  • Author(s): 槙田紀子, 佐藤純一郎, 間中勝則, 矢嶋由紀, 大石篤郎, 橋本真紀子, 藤田敏郎, 飯利太朗
  • Organizer: 第46回日本臨床分子医学会
  • Place of Presentation: 神戸
• [Presentation] 後天性低カルシウム尿性高カルシウム血症で発見されたカルシウム感知受容体自己抗体の作用機構の解析 (2008)
  • Author(s): 槙田紀子, 佐藤純一郎, 間中勝則, 矢嶋由紀, 大石篤郎, 橋本真紀子, 藤田敏郎, 飯利太朗
  • Organizer: 第46回日本臨床分子医学会
  • Place of Presentation: 神戸
• [Presentation] 後天性低カルシウム尿性高カルシウム血症症例で発見されたCa感知受容体に対する自己〓 (2007)
  • Author(s): 槙田紀子、飯利太朗 等
  • Organizer: 日本内分泌学会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2007-06-14
• [Presentation] 後天性低カルシウム尿性高カルシウム血症で発見されたカルシウム感知受容体自己抗体の作用機構の解析 (2007)
  • Author(s): 槙田紀子, 佐藤純一郎, 間中勝則, 矢嶋由紀, 大石篤郎, 橋本真紀子, 藤田敏郎, 飯利太朗
  • Organizer: 第80回日本内分泌学会
  • Place of Presentation: 東京
• [Book] Gタンパク質共役受容体 高血圧 (日本臨床増刊号) (2009)
  • Author(s): 槙田紀子, 飯利太朗
• [Book] Gタンパク質遺伝子 高血圧 (2009)
  • Author(s): 間中勝則, 槙田紀子, 飯利太朗
• [Book] 高血圧 (2009)
  • Author(s): 槙田紀子, 飯利太朗(分担)
  • Total Pages: 521
  • Publisher: 日本臨床社
• [Book] アルドステロン研究の新展開 (2008)
  • Author(s): 槙田紀子分担 飯利太朗編
  • Total Pages: 125
  • Publisher: 医歯薬出版
• [Book] 巻頭言 特集 : アルドステロン研究の新展開 (飯利太朗 編)医学のあゆみ (2007)
  • Author(s): 飯利太朗
  • Total Pages: 689
• [Book] アルドステロン研究の理解に必要な基礎知識 (臨床編)医学のあゆみ (2007)
  • Author(s): 槙田紀子
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