Novel mechanisms of growth regulation through changes in ubiquitination of insulin receptor substrates

• Project/Area Number: 22248030
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied animal science
• Research Institution: The University of Tokyo
• Principal Investigator: TAKAHASHI Shin-Ichiro 東京大学, 農学生命科学研究科, 准教授 (00197146)
• Co-Investigator(Kenkyū-buntansha): HAKUNO Fumihiko 東京大学, 大学院農学生命科学研究科, 助教 (30282700) ; NISHIHARA Masugi 東京大学, 大学院農学生命科学研究科, 教授 (90145673) ; ITO Akihiro 独立行政法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (40391859) ; YASUSHI Saeki 公益財団法人東京都医学総合研究所, 吉田化学遺伝学研究室, 主席研究員 (80462779)
• Project Period (FY): 2010-05-31 – 2013-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥46,020,000 (Direct Cost: ¥35,400,000、Indirect Cost: ¥10,620,000); Fiscal Year 2012: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000); Fiscal Year 2011: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2010: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
• Keywords: 代謝・内分泌制御 / インスリン様成長因子 / インスリン受容体基質 / ユビキチン化酵素 / 脱ユビキチン化酵素 / 細胞内シグナル / インスリン様活性 / ユビキチンリガーゼ / アダプタータンパク質 / インスリン / インスリン様成長因子受容体 / 増殖

Research Abstract

Insulin receptor substrates (IRSs) that are phosphorylated by insulin-like growth factor (IGF)-I receptor tyrosine kinases. Phosphotyrosyl IRSs are recognized by signaling molecules possessing SH2 domains, which mediate various IGF bioactivities. However, we have shown that IRSs are also associated with other proteins by a phosphotyrosine-independent mechanism. These protein complexes contain a number of ubiquitin ligases (E3) and deubiquitinating enzymes (DUBs). Our results indicate that ubiquitination of IRSs which was dynamically regulated by these E3 and DUBs in response to other extracellular factor, plays important roles not only in regulation of their protein levels but also modulation of their tyrosine phosphorylation, leading to control of IGF bioactivities, such as a growth-promoting activity.

Research Products

• [Journal Article] Steroid hormones are novel nucleoside transport inhibitors by competition with nucleosides for their transporters. (2014)
  • Author(s): Kaneko M, Hakuno F, Kamei H, Yamanaka D, Chida K, Minami S, Coe RI, Takahashi S-I.
  • Journal Title: Bicohem Biophysic Res Commun. Volume: 443 Issue: 2 Pages: 505-510
  • DOI: 10.1016/j.bbrc.2013.11.132
  • Peer Reviewed
• [Journal Article] Insulin receptor substrate-1 associates with small nucleolar RNA which contributes to ribosome biogenesis. (2014)
  • Author(s): Ozoe A, Sone M, Fukushima T, Kataoka N, Chida K, Asano T, Hakuno F, Takahashi S-I.
  • Journal Title: Frontiers in Endocrinology Volume: 5 Pages: 24-24
  • DOI: 10.3389/fendo.2014.00024
  • Peer Reviewed / Open Access
• [Journal Article] Tissue-specific effects of protein malnutrition on insulin signaling pathway and lipid accumulation in growting rats. (2014)
  • Author(s): Toyoshima Y, Tokita R, Taguchi Y, Akiyama-Akanishi N, Takenaka A, Kato H, Chida K, Hakuno F, Minami S, Takahashi S-I.
  • Journal Title: Endocrine J. Volume: 61 Pages: 499-512
• [Journal Article] 解説:インスリン様活性と高齢化社会で克服すべき疾病 (2013)
  • Author(s): 高橋伸一郎、伯野史彦、亀井宏泰、Leonard Girnita、Ignacio Torres-Aleman、東祐輔、福嶋俊明、柴野卓志、尾添淳文、山中大介
  • Journal Title: 化学と生物 Volume: 51 Pages: 389-399
  • URL: http://www.jsbba.or.jp/pub/journal_kasei/
  • Peer Reviewed
• [Journal Article] Something old, something new and something borrowed; emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation (2013)
  • Author(s): Girnita L, Worrall C, Takahashi S-I, Seregard S, Girnita A
  • Journal Title: Cell. Mol. Life Sci. Volume: なし Issue: 13 Pages: 2403-2427
  • DOI: 10.1007/s00018-013-1514-y
  • Peer Reviewed / Open Access
• [Journal Article] Insulin Receptor Substrate-1 (IRS-1) Forms a Ribonucleoprotein Complex Associated with Polysomes (2013)
  • Author(s): Ozoe A, Sone M, Fukushima T, Kataoka N, Arai T, Chida K, Asano T, Hakuno F, Takahashi S-I
  • Journal Title: FEBS Lett. Volume: 587(15) Issue: 15 Pages: 2319-24
  • DOI: 10.1016/j.febslet.2013.05.066
  • Peer Reviewed
• [Journal Article] The AP-1 complex regulates intracellular localization of insulin receptor substrate 1, which is required for insulin-like growth factor I-dependent cell proliferation (2013)
  • Author(s): Yosuke Yoneyama
  • Journal Title: Molecular and Cellular Biology Volume: Volume 33 Issue: 10 Pages: 1991-2003
  • DOI: 10.1128/mcb.01394-12
  • Peer Reviewed
• [Journal Article] 解説：インスリン様活性と高齢化社会で克服すべき疾病 (2013)
  • Author(s): 高橋伸一郎、伯野史彦、亀井宏泰、Leonard Girnita、Ignacio Torres-Aleman、東祐輔、福嶋俊明、柴野卓志、尾添淳文、山中大介
  • Journal Title: 化学と生物 Volume: 51 Pages: 389-399
  • Peer Reviewed
• [Journal Article] 酸化ストレスとインスリン様活性の相互作用が健康寿命延伸に果たす役割 (2013)
  • Author(s): 高橋伸一郎、金子元、竹中麻子、東祐輔、尾添淳文、伯野史彦
  • Journal Title: 医学のあゆみ Volume: 247 Pages: 934-941
• [Journal Article] Insulin/insulin-like growth factor (IGF) stimulation abrogates an association between a deubiquitinating enzyme USP7 and insulin receptor substrates (IRSs) followed by proteasomal degradation of IRSs (2012)
  • Author(s): Yoshihara H, Fukushima T, Hakuno F, Saeki Y, Tanaka K, Ito A, Yoshida M, Iemura S, Natsume T, Asano T, Chida K, Girnita L, Takahashi S-I
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 423 Issue: 1 Pages: 122-127
  • DOI: 10.1016/j.bbrc.2012.05.093
  • Peer Reviewed
• [Journal Article] Phosphatidylinositol 3-kinase binding protein, PITKAP/XB130 is required for cAMP-induced amplification of IGF mitogenic activity in FRTL-5 thyroid cells. (2012)
  • Author(s): Yamanaka D, Akama T, Fukushima T, Nedachi T, Kawasaki C, Chida K, Minami S, Suzuki K, Hakuno F, Takahashi S-I.
  • Journal Title: Mol Endocrinol Volume: 26 Issue: 6 Pages: 1043-1055
  • DOI: 10.1210/me.2011-1349
  • Peer Reviewed
• [Journal Article] Phosphatidylinsitol 3-kinase (PI3K) activity bound to insulin-like growth factor-I (IGF-I) receptor, which is continuously sustained by IGF-I stimulation, is required for IGF-I-induced cell proliferation. (2012)
  • Author(s): Fukushima T, Nakamura Y, Yamanaka D, Shibano T, Chida K, Minami S, Asano T, Hakuno F, Takahashi S-I.
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 35 Pages: 29713-29721
  • DOI: 10.1074/jbc.m112.393074
  • Peer Reviewed
• [Journal Article] Constitutive expression of insulin receptor substrate(IRS)-1 inhibits myogenic differentiation through nuclear exclusion of Foxo1 in L6 myoblasts (2011)
  • Author(s): Hakuno F, Yamauchi Y, Kaneko G, Yoneyama Y, Nakae J, Chida K, Kadowaki T, Yamanouchi K, Nishihara M, Takahashi S
  • Journal Title: PLoS ONE Volume: 6 Issue: 10 Pages: e25655-e25655
  • DOI: 10.1371/journal.pone.0025655
  • Peer Reviewed
• [Journal Article] HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells (2011)
  • Author(s): Fukushima T, Okajima H, Yamanaka D, Ariga M, Nagata S, Ito A, Yoshida H, Asano T, Chida K
  • Journal Title: Mol.Cell Endocrinol. Volume: 344 Issue: 1-2 Pages: 81-90
  • DOI: 10.1016/j.mce.2011.06.029
  • Peer Reviewed
• [Journal Article] Insulin receptor substrates form high-molecular-mass complexes that modulate their availability to insulin/insulin-like growth factor-I receptor tyrosine kinases (2011)
  • Author(s): Fukushima T, Arai T, Ariga M, Okajima H, Ooi Y, Iijima Y, Sone M, Cho Y, Ando Y, Kasahara K, Ozoe A, Yoshihara H, Chida K, Okada S, Kopchick JJ, Hakuno F, Takahashi S-I
  • Journal Title: Biochem Biophys Res Commun. Volume: 404 Issue: 3 Pages: 767-773
  • DOI: 10.1016/j.bbrc.2010.12.045
  • Peer Reviewed
• [Journal Article] Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with IRS-1 and enhances insulin actions and adipogenesis (2011)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 286 Issue: 23 Pages: 20812-20822
  • DOI: 10.1074/jbc.m110.206904
  • Peer Reviewed
• [Journal Article] Insulin receptor substrates form high-molecular-mass complexes that modulate their availability to insulin/insulin-like growth factor-I receptor tyrosine kinases (2011)
  • Author(s): Fukushima T, Takahashi S-I, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 404 Pages: 767-773
  • Peer Reviewed
• [Journal Article] Insulin receptor substrate-3, interacting with Bcl-3, enhances p50 NF-κB activity (2010)
  • Author(s): Kabuta T, Takahashi S-I, et al
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 394 Pages: 697-702
  • Peer Reviewed
• [Journal Article] Paraquat-induced oxidative stress represses PI 3-kinase activities leading to impaired glucose uptake in 3T3-L1 adipocytes (2010)
  • Author(s): Shibata M, Takahashi S-I, et al
  • Journal Title: J Biol Chem Volume: 285 Pages: 20916-20925
  • Peer Reviewed
• [Journal Article] Dietary protein deprivation up-regulates insulin signaling and inhibits gluconeogenesis in rat liver (2010)
  • Author(s): Toyoshima Y, Takahashi S-I, et al
  • Journal Title: J Mol Endocrinol Volume: 45 Pages: 329-340
  • Peer Reviewed
• [Journal Article] 発達と成長を司るホルモン、インスリン様成長因子 (2010)
  • Author(s): 高橋伸一郎, ら
  • Journal Title: 日本未熟児新生児学会雑誌 Volume: 22 Pages: 19-25
  • NAID: 10026440072
• [Presentation] Regulation of intracellular localization of insulin receptor substrate (IRS) proteins and insulin-like activities. Obesity, Diabetes and Cancer (2013)
  • Author(s): Shin-Ichiro Takahashi
  • Organizer: the roles of insulin and insulin-like growth factors
  • Place of Presentation: Taormina, Italy
  • Year and Date: 2013-08-04
  • Invited
• [Presentation] 物質代謝制御におけるインスリン様成長因子とインスリンの連携 (2013)
  • Author(s): 高橋伸一郎
  • Organizer: 低タンパク質栄養状態に応答したタンパク質代謝と糖代謝の内分泌制御シンポジウム「栄養と内分泌・代謝」第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
  • Year and Date: 2013-04-27
  • Invited
• [Presentation] A deubiquitinating enzyme, USP7, is associated with insulin receptor substrate (IRS)-2 forming a negative feedback loop in insulin/IGF signaling (2013)
  • Author(s): Hidehito Yoshihara, Toshikai Fukushima, Furuta Haruka, Fumihiko Hakuno, Yasushi Saeki, Keiji Tanaka, Akihiro Ito, Shunichiro Iemura, Tohru Natsume, Shin-Ichiro Takahashi
  • Organizer: EMBO Conference"Ubiquitin and ubiquitin-like proteins : from structure to function
  • Place of Presentation: Riva del Garda, Italy
• [Presentation] Constitutive IRS-1 expression suppressed cell invasion, leading to inhibition of myogenesis in L6 myoblasts (2013)
  • Author(s): Fumihiko Hakuno and Shin-Ichiro Takahashi
  • Organizer: Gordon Research Conference: Insulin-like growth factors in physiology and disease
  • Place of Presentation: Ventura, CA, USA
• [Presentation] Identification of proteins proximal to insulin receptor substrate (IRS)-1 in the intracellular vesicle compartment (2013)
  • Author(s): Yosuke Yoneyama, Akihiro Ito, Kazuhiro Chida, Minoru Yoshida, Fumihiko Hakuno, Shin-Ichiro Takahashi
  • Organizer: Gordon Research Conference: Insulin-like growth factors in physiology and diseases
  • Place of Presentation: Ventura, CA, USA
• [Presentation] Phosphoglycerate-mutase 5 (PGAM5) is involved in dephosphorylation of insulin receptor substrates (IRSs) and controlling insulin-like activities (2013)
  • Author(s): Junichi Inobe, Toshiaki Fukushima, Akihiro Ito, Yukako Kida, Takashi Shiano, Kazuhiro Chida, Minoru Yoshida, Tomoichiro Asano, Kouske Takeda, Fumihiko Hakuno, Shin-Ichiro Takahashi
  • Organizer: Gordon Research Conference: Insulin-like growth factors in physiology and diseases
  • Place of Presentation: Ventura, CA, USA
• [Presentation] A deubiquitinating enzyme, USP7, is associated with insulin receptor substrate (IRS)-2 forming a negative feedback loop in insulin/IGF signaling (2013)
  • Author(s): Hidehito Yoshihara, Toshikai Fukushima, Furuta Haruka, Fumihiko Hakuno, Yasushi Saeki, Keiji Tanaka, Akihiro Ito, Shunichiro Iemura, Tohru Natsume, Takahashi Shin-Ichiro
  • Organizer: EMBO Conference “Ubiquitin and ubiquitin-like proteins: from structure to function
  • Place of Presentation: Riva del Garda, Italy
• [Presentation] Ubiquitin ligase Nedd4 interacts with insulin receptor substrate (IRS)-2 in response to humoral/nutritional stimuli, thereby enhancing IRS-2-mediated IGF/insulin signals through a novel mechanism (2012)
  • Author(s): Toshiaki Fukushima, Hidehito Yoshihara, Fumihiko Hakuno, Yasushi Saeki, Keiji Tanaka, Akihiro Ito, Minoru Yoshida, Kazuhiro Chida, Hideyuki Sakoda, Tomoichiro Asano, and Shin-Ichiro Takahashi
  • Organizer: The 6th Interntional Congress of the GRS-IGF Society
  • Place of Presentation: Munich, Germany
  • Year and Date: 2012-10-20
• [Presentation] AP-1 complex regulates intracellular localization of insulin receptor substrate-1 required for insulin-like growth factor-I-dependent proliferation (2012)
  • Author(s): Yosuke Yoneyama, Satoshi Yoshinaga, Masao Matsuo, Kazumi Take, Tomohiro Kabuta, Kazuhiro Chida, Fumihiko Hakuno, Shin-Ichiro Takahashi
  • Organizer: The 6th Interntional Congress of the GRS-IGF Society
  • Place of Presentation: Munich, Germany
  • Year and Date: 2012-10-18
• [Presentation] 肝細胞においてNedd4はインスリン受容体基質(IRS)-2のユビキチン化を介してインスリンシグナルを増強する (2011)
  • Author(s): 福嶋俊明,吉原英人,伯野史彦,佐伯泰,田中啓二,伊藤昭博,中津祐介,鎌田英明,高橋伸一郎,浅野知一郎
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都(口頭発表、ポスター発表)
  • Year and Date: 2011-09-23
• [Presentation] インスリン様成長因子とインスリンの単独プレイと連携プレイ (2011)
  • Author(s): 高橋伸一郎
  • Organizer: 第29回内分泌サマーセミナー
  • Place of Presentation: 東北大学、仙台
  • Year and Date: 2011-07-07
  • Invited
• [Presentation] Ubiquitin ligase Nedd4 recruits insulin receptor substrate (IRS)-2 to membrane fractions, enhancing IRS-2-mediated signals followed by mitogenic bioactivity of insulin-like growth factors (IGFs) (2011)
  • Author(s): Toshiaki Fukushima, Hidehito Yoshihara, Fumihiko Hakuno, Yasushi Saeki, Keiji Tanaka, Kazuhiro Chida, Tomoichiro Asano, Shin-Ichiro Takahashi
  • Organizer: Gordon Research Conference"Insulin-like Growth Factors in Physiology & Disease"
  • Place of Presentation: Ventura CA, USA
  • Year and Date: 2011-05-01
• [Presentation] Ubiquitin ligase Nedd4 recruits insulin receptor substrate (IRS)-2 to membrane fractions, enhancing IRS-2-mediated signals followed by mitogenic bioactivity of insulin-like growth factors (IGFs) (2011)
  • Author(s): Toshiaki Fukushima, et al
  • Organizer: Gordon Research Conference "Insulin-like Growth Factors in Physiology & Disease"
  • Place of Presentation: Ventura CA, USA
  • Year and Date: 2011-03-01
• [Presentation] 低タンパク質食を給餌したラット肝臓に中性脂肪蓄積を引き起こす内分泌系およびインスリンシグナルの変動 (2011)
  • Author(s): 豊島由香
  • Organizer: 第65回日本栄養・食糧学会大会
  • Place of Presentation: 東京
• [Presentation] Nedd4によるインスリン受容体基質(IRS)のユビキチン化はインスリン・IGF-Iシグナルを増強する (2011)
  • Author(s): 福嶋俊明
  • Organizer: 日本生化学会中国四国支部例会
  • Place of Presentation: 広島
• [Presentation] Repression of GKAP (cGMP-dependent kinase anchoring protein) causes insulin resistance in 3T3-L1 adipocytes (2011)
  • Author(s): Yasutoshi Ando
  • Organizer: ENDO2011 The 93rd Annual Meeting of the Endocrine Society
  • Place of Presentation: Boston
• [Presentation] ユビキチンリガーゼNedd4はインスリン受容体基質(IRS)-2の粗膜画分への移行を促進し、IGFシグナルおよび増殖活性を増強する (2010)
  • Author(s): 福嶋俊明, ら
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会・BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] インスリン受容体基質(IRS)と脱ユビキチン化酵素USP7の相互作用機構 (2010)
  • Author(s): 吉原英人, ら
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会・BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] IGF活性を修飾する機構の多様性 (2010)
  • Author(s): 高橋伸一郎
  • Organizer: Forum on Grwoth Hormone Research 2010
  • Place of Presentation: 東京
  • Year and Date: 2010-11-06
• [Presentation] Effects of oxidative stress on insulin signaling and bioactivities (2010)
  • Author(s): Shin-Ichiro Takahashi
  • Organizer: The 26th Kumamoto Medical Bioscience Symposium
  • Place of Presentation: Kumamoto
  • Year and Date: 2010-06-19
• [Presentation] 進化から学ぶIGF/インスリンシステムの生理的意義 (2010)
  • Author(s): 高橋伸一郎
  • Organizer: GH/IGF-I & Longevity Meeting
  • Place of Presentation: 東京
  • Year and Date: 2010-04-17
• [Presentation] Suppression of insulin signaling in white adipose tissues contributes to preferential lipid accumulation in liver under conditions of protein malnutrition (2010)
  • Author(s): Yuka Toyoshima, et al
  • Organizer: The 5th International Congress of GRS and IGF Society
  • Place of Presentation: New York, USA
• [Presentation] Continuous activation of IGF signaling inhibits myogenic differentiation of L6 myoblasts (2010)
  • Author(s): Fumihiko Hakuno, et al
  • Organizer: The 5th International Congress of GRS and IGF Society
  • Place of Presentation: New York, USA
• [Presentation] Insulin receptor substrate-1 localized around endosomes, sorted by adaptor protein-1 complex, transmits insulin/IGF signals to specific Akt substrates (2010)
  • Author(s): Yosuke Yoneyama, et al
  • Organizer: The 5th International Congress of GRS and IGF Society
  • Place of Presentation: New York, USA
• [Presentation] PI 3-kinase activation through c-Src-dependent tyrosine phosphorylation of PITKAP/XB130, a novel binding partner of a PI 3-kinase p85 regulatory subunit, plays novel roles in priming cells to IGF (2010)
  • Author(s): Daisuke Yamanaka, et al
  • Organizer: The 5th International Congress of GRS and IGF Society
  • Place of Presentation: New York, USA
• [Presentation] 新規PI 3-kinase結合タンパク質PI3KAP/XB130は、TSHとIGFによる甲状腺細胞の相乗的増殖誘導に必須である
  • Author(s): 山中大介、赤間剛、福嶋俊明、南史朗、伯野史彦、高橋伸一郎
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 動物の一生におけるインスリン様活性の役割
  • Author(s): 高橋伸一郎
  • Organizer: 第8回アンチエイジング静岡コンファレンス
  • Place of Presentation: 静岡
  • Invited
• [Presentation] Regulation of insulin-like activities and their physiological significance
  • Author(s): Shin-Ichiro Takahashi
  • Organizer: International Seminar “Insulin-like activities and their related-diseases in aging from the aspects of basic and translational medicine”
  • Place of Presentation: 東京
• [Presentation] Insulin receptor substrates (IRSs) form complex with Ras-GAP SH3-domain-binding protein 1 (G3BP1), regulating cap-independent translation of Bcl-2 mRNA.
  • Author(s): Atufumi Ozoe, Meri Sone, Toshiaki Fukushima, Naoyuki Kataoka, Kazuhiro Chida, Fumihiko Hakuno, Shin-Ichiro Takahashi
  • Organizer: The 6th Interntional Congress of the GRS-IGF Society
  • Place of Presentation: Munich, Germany
• [Presentation] Phosphatidylinositol 3-kinase-binding protein, PI3KAP/XB130 crosslinks actin filaments and regulates cell migration
  • Author(s): Daisuke Yamanaka, Takeshi Akama, Fumihiko Hakuno, Kazuhiro Chida, Kouichi Suzuki, Shiro Minami, and Shin-Ichiro Takahashi
  • Organizer: The 6th Interntional Congress of the GRS-IGF Society
  • Place of Presentation: Munich, Germany
• [Presentation] A deubiquitinating enzyme, USP7, is associated with insulin receptor substrate (IRS)-2 forming a negative feedback loop in insulin/IGF signaling
  • Author(s): Hidehito Yoshihara, Toshiaki Fukushima, Fumihiko Hakuno, Yasushi Saeki, Keiji Tanaka, Akihiro Ito, Minoru Yoshida, Shunichiro Iemura, Tohru Natsume, Tomoichiro Asano, Kazuhiro Chida, Leonard Girnita, and Shin-Ichiro Takahashi
  • Organizer: The 6th Interntional Congress of the GRS-IGF Society
  • Place of Presentation: Munich, Germany
• [Presentation] インスリン受容体基質―Rabankyrin-5複合体がインスリン様成長因子で誘導されるマクロピノサイトーシスに果たす役割の検討
  • Author(s): 矢野貴之、米山鷹介、松井利晃、岡嶋裕志、千田和広、伯野史彦、高橋伸一郎
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、福岡
• [Presentation] インスリン受容体基質はG3BP1と相互作用し、cap非依存的なBcl-2 mRNAの翻訳を正に制御する
  • Author(s): 尾添淳文、曽根芽里、福嶋俊明、片岡直行、浅野知一郎、千田和広、伯野史彦、高橋伸一郎
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、福岡
• [Presentation] 物質代謝制御におけるインスリン様成長因子とインスリンの連携：低タンパク質栄養状態に応答したタンパク質代謝と糖代謝の内分泌制御
  • Author(s): 高橋伸一郎
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] Roles of Insulin Receptor Substrate Complexes Containing Rabankyrin-5 in Insulin-Like Growth Factor-I-Induced Macropinocytosis
  • Author(s): Takayuki Yano, Yosuke Yoneyama, Toshiaki Matsui, Hiroshi Okajima, Kazuhiro Chida, Fumihiko Hakuno, Shin-Ichiro Takahashi
  • Organizer: ENDO2013
  • Place of Presentation: San Francisco, USA
• [Presentation] Molecular mechanisms of potentiation of insulin-like growth factors (IGFs) bioactivities by other extracellular factors
  • Author(s): Shin-Ichiro Takahashi
  • Organizer: Invited seminar of Arizona State University
  • Place of Presentation: Tempe, Phoenix, USA
  • Invited
• [Presentation] IRSome: novel complexes to mediate/modulate insulin-like activities
  • Author(s): Shin-Ichiro Takahashi
  • Organizer: INTERNATIONAL OPEN WORKSHOP “Emerging Paradigms of Insulin-Like Activities in Physiology & Disease: From Pathophysiology to Targeted Therapy”
  • Place of Presentation: Stockholm, Sweden
  • Invited
• [Presentation] Regulation of intracellular localization of insulin receptor substrate (IRS) proteins and insulin-like activities
  • Author(s): Shin-Ichiro Takahashi
  • Organizer: Obesity, Diabetes and Cancer: the roles of insulin and insulin-like growth factors
  • Place of Presentation: Taormina, Italy
  • Invited
• [Presentation] インスリン様成長因子とインスリンの単独プレイと連携プレイ
  • Author(s): 高橋伸一郎
  • Organizer: 第29回内分泌サマーセミナー
  • Place of Presentation: 仙台
  • Invited
• [Presentation] Nedd4はインスリン受容体基質（IRS）-2のユビキチン化を介してインスリンシグナルを増強する
  • Author(s): 福嶋俊明
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] インスリン様ペプチドの進化と生理的意義
  • Author(s): 高橋伸一郎
  • Organizer: 第29回千駄木内分泌懇話会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 成長ホルモンによるインスリン抵抗性発生機構とその補償機構
  • Author(s): 高橋伸一郎
  • Organizer: 第15回日本内分泌病理学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Interaction between insulin receptor substrates (IRSs) and various proteins including diacylglycerol kinase  (DGK) modulates insulin bioactivities
  • Author(s): Shin-Ichiro Takahashi
  • Organizer: Post-International Conference on Food Factors (ICoFF) Workshop “Food Factors forPreventing the Metabolic Syndrome”
  • Place of Presentation: Tainan
  • Invited
• [Presentation] インスリン受容体基質（IRS）はミトコンドリアにも存在し、インスリン様成長因子（IGF）のシグナル伝達・活性発現に関与している
  • Author(s): 吉永聖
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] アミノ酸欠乏やインスリン欠乏が培養肝細胞のインスリン様成長因子システムおよびインスリン応答性に及ぼす影響の解析
  • Author(s): 赤西 成美
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都
• [Book] 「農学入門」第三部10章「農学と動物科学:巨大な細胞社会を統御する仕組みを知り利用する」(249-279) (2013)
  • Author(s): 高橋伸一郎
  • Publisher: 養賢堂
• [Book] 農学入門 (2013)
  • Author(s): 高橋伸一郎
  • Total Pages: 30
  • Publisher: 養賢堂
• [Remarks] 生体の生命維持に必須な細胞内シグナルのクロストークを科学する
  • URL: http://endo.ar.a.u-tokyo.ac.jp/index0.html
• [Remarks] 生体の生命維持に必須な細胞内シグナルの クロストークを科学する
  • URL: http://endo.ar.a.u-tokyo.ac.jp/shingroup/index.html
• [Remarks] 生体の生命維持に必須な細胞内シグナルの クロストークを科学する
  • URL: http://endo.ar.a.u-tokyo.ac.jp/index0.html
• [Remarks]
  • URL: http://endo.ar.a.u-tokyo.ac.jp/lab/shingroup/index.html