Analysis of the regulatory mechanisms of G protein-coupled receptor signaling

• Project/Area Number: 25293013
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Itoh Hiroshi 奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (10183005)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Tetsuo 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (80433994)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: Gタンパク質 / GPCR / シグナル伝達 / 制御分子

Outline of Final Research Achievements

We generated agonistic monoclonal antibodies against GPR56 and showed that the antibodies inhibit the migration of human glioma cells through Gq, Rho, and Rho kinase pathway. We found the possibility that GPR56 transmembrane region and latrophilin1 extracellular region forms a chimera receptor in GABAegic neurons, and latrotoxin, a latrophilin1 ligand, induces cell response mediated by the chimera receptor. We demonstrated that Ric-8 functions as a positive regulator for GPCR signaling system by regulating two post-translational modifications, ubiquitination and palmitoylation, on G proteins.

Research Products

• [Journal Article] Light-dependent activation of G proteins by two isoforms of chicken melanopsins. (2015)
  • Author(s): Masaki Torii, Daisuke Kojima, Akiyuki Nishimura Hiroshi Itoh, Yoshitaka Fukada
  • Journal Title: Photochem. Photobiol. Sci. Volume: 14 Issue: 11 Pages: 1991-1997
  • DOI: 10.1039/c5pp00153f
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 三量体Gタンパク質 (2015)
  • Author(s): 堀部修平 伊東 広
  • Journal Title: 生体の科学「細胞シグナル操作法」 Volume: 66 Pages: 400-401
  • NAID: 10024383659
  • Peer Reviewed
• [Journal Article] Agonistic Antibodies Reveal the Function of GPR56 in Human Glioma U87-MG Cells (2015)
  • Author(s): Ohta S, Sakaguchi S, Kobayashi Y, Mizuno N, Tago K, Itoh H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 4 Pages: 594-600
  • DOI: 10.1248/bpb.b14-00752
  • NAID: 130005062265
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5. (2015)
  • Author(s): Tago K,Funakoshi-Tago M, Itoh H, Furukawa Y, Kikuchi J, Kato T, Suzuki K,Yanagisawa K
  • Journal Title: Oncogene Volume: 34 Pages: 314-322
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5. (2014)
  • Author(s): Tago K, Funakoshi-Tago M, Itoh H, Furukawa Y, Kikuchi J, Kato T, Suzuki K, Yanagisawa K
  • Journal Title: Oncogene Volume: 未定 Issue: 3 Pages: 310-318
  • DOI: 10.1038/onc.2013.561
  • Peer Reviewed / Open Access
• [Journal Article] Increased ubiquitination and the crosstalk of G protein signaling in cardiac myocytes: Involvement of Ric-8B in Gs suppression by Gq signal (2013)
  • Author(s): Riris Jenie, Motoki Nishimura, Mika Fujino, Michio Nakaya, Norikazu Mizuno, Kenji Tago, Hitoshi Kurose & Hiroshi Itoh.
  • Journal Title: Genes to Cells Volume: 18 Issue: 12 Pages: 1095-1106
  • DOI: 10.1111/gtc.12099
  • Peer Reviewed
• [Journal Article] 三量体Gタンパク質シグナル制御機構の新たなる展開 (2013)
  • Author(s): 伊東 広 他
  • Journal Title: 生化学 Volume: 85 Pages: 531-542
  • NAID: 10031190082
  • Peer Reviewed
• [Presentation] Gαsユビキチン修飾を制御する分子機構の解析 (2015)
  • Author(s): 鯉森貴行, 西村基喜, 竹田浩之, 多胡憲治, 小林 哲夫, 澤崎達也, 伊東 広
  • Organizer: 第38回日本分子生物学会年会・第88回日本生化学大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Two isoforms of chicken melanopsin activate mutually different subtypes of G protein in light-dependent manners. (2015)
  • Author(s): 鳥居 雅樹, 小島 大輔, 西村 明幸, 伊東 広, 深田 吉孝
  • Organizer: 第38回日本分子生物学会年会・第88回日本生化学大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Regulation of G protein-coupled receptor signal in cancer cells (2015)
  • Author(s): Itoh H
  • Organizer: Pontianak International Conference on Advanced Pharmaceutical Sciences (PICAPS) 2015 and the 6th Annual Symposium of Indonesian Society for Cancer Chemoprevention
  • Place of Presentation: Pontianak, Indonesia
  • Year and Date: 2015-09-14
  • Int'l Joint Research / Invited
• [Presentation] Analysis of melecular mechanisms for Gαs ubiquitination (2015)
  • Author(s): Koimori T, Nishimura M, Takeda H, Tago K, Kobayashi T, Sawazaki T, Itoh H
  • Organizer: Pontianak International Conference on Advanced Pharmaceutical Sciences (PICAPS) 2015 and the 6th Annual Symposium of Indonesian Society for Cancer Chemoprevention
  • Place of Presentation: Pontianak, Indonesia
  • Year and Date: 2015-09-14
  • Int'l Joint Research
• [Presentation] Analysis of serotonin signaling mediated through primary cilia (2015)
  • Author(s): Dateyama I, Kobayashi T, Itoh H
  • Organizer: The 4th International Conference on Pharmacy and Advanced Pharmaceutical Sciences
  • Place of Presentation: Yogyakarta, Indonesia
  • Year and Date: 2015-09-07
  • Int'l Joint Research
• [Presentation] The role of Ric-8A and Gαi signaling in spindle formation (2015)
  • Author(s): Horibe S, Kaji N, Kobayashi T, Itoh H
  • Organizer: International Conference on Biosciences (IcoBio)
  • Place of Presentation: Bogor, Indonesia
  • Year and Date: 2015-08-06
  • Int'l Joint Research
• [Presentation] 紡錘体形成におけるRic-8とGαiシグナルの役割 (2015)
  • Author(s): 堀部修平, 梶 紀子, 小林 哲夫, 伊東 広
  • Organizer: 第67回日本細胞生物学会
  • Place of Presentation: タワーホール船場（東京都江戸川区）
  • Year and Date: 2015-06-30
• [Presentation] Analysis of molecular mechanism for Gαs ubiquitination (2014)
  • Author(s): Koimori Takayuki, Tetsuo Kobayashi, Hiroshi Itoh
  • Organizer: The 2014 ASCB meeting
  • Place of Presentation: Philadelphia, U.S.A.
  • Year and Date: 2014-12-06 – 2014-12-10
• [Presentation] Gタンパク質共益受容体GPR56の結合分子Leprecan1の解析 (2014)
  • Author(s): 小坂 隆二, 岩崎 剛, 中村 陽介, 松田 直樹, 多胡 憲治, 小林 哲夫, 伊東 広
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 一次繊毛におけるRab-likeファミリータンパク質群の機能解析 (2014)
  • Author(s): 太田 麗央, 小林 哲夫, 伊東 広
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 膵管癌細胞における一次繊毛消失機構の解析 (2014)
  • Author(s): 中薗 昴亮, 小林 哲夫, 徳田 澪, Brian David Dynlacht, 伊東 広
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 新規がん抑制遺伝子産物TRB3はkB-Ras のSUMO化を介してRas(G12V)の発がんシグナルを制御する (2014)
  • Author(s): 多胡 憲治, 多胡 めぐみ, 杉山 直幸,伊東 広,柳澤 健
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 一次繊毛を介したセロトニンシグナル伝達機構の解析 (2014)
  • Author(s): 伊達山 泉, 小林 哲夫, 伊東 広
  • Organizer: 第66回日本細胞生物学会
  • Place of Presentation: 奈良県新公会堂、奈良県奈良市
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] 機能抗体を用いた癌細胞におけるGPR56の機能解析 (2014)
  • Author(s): 水野 憲一, 太田 茂之, 小林 祐希, 坂口 さや香, 伊東 広
  • Organizer: 第66回日本細胞生物学会
  • Place of Presentation: 奈良県新公会堂、奈良県奈良市
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] 心筋細胞のGタンパク質シグナルにおけるRic-8Bの機能 (2013)
  • Author(s): Riris I . Jenie et al.
  • Organizer: 第86回 日本生化学会大会
  • Place of Presentation: 横浜、神奈川
• [Presentation] 神経細胞の分化に伴うGPR56の発現パターンの変化 (2013)
  • Author(s): 野島悠佑 他
  • Organizer: 第36回 日本分子生物学会年会
  • Place of Presentation: 神戸、兵庫
• [Presentation] Gαsユビキチン修飾を制御する分子機構の解析 (2013)
  • Author(s): 鯉森貴行 他
  • Organizer: 第36回 日本分子生物学会年会
  • Place of Presentation: 神戸、兵庫
• [Presentation] LGRの発現とシグナル伝達の解析 (2013)
  • Author(s): 根岩直希 他
  • Organizer: 第36回 日本分子生物学会年会
  • Place of Presentation: 神戸、兵庫
• [Presentation] 膵管細胞における一次繊毛消失メカニズムの解析 (2013)
  • Author(s): 小林哲夫 他
  • Organizer: 第36回 日本分子生物学会年会
  • Place of Presentation: 神戸、兵庫