Functional analysis of the C-treminal frangment of membrane-anchored growth factors

• Project/Area Number: 17014068
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Ehime University
• Principal Investigator: HIGASHIYAMA Shigeki Ehime University, 大学院・医学系研究科, 教授 (60202272)
• Co-Investigator(Kenkyū-buntansha): MORIMOTO Chie 安田女子大学, 薬学部, 講師 (10332826) ; HIEDA Miki 大阪大学, 大学院・医学系研究科, 特任助教 (00380254) ; INOUE Hirofumi 愛媛大学, 大学院・医学系研究科, 講師 (70321635)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥55,300,000 (Direct Cost: ¥55,300,000); Fiscal Year 2009: ¥11,000,000 (Direct Cost: ¥11,000,000); Fiscal Year 2008: ¥11,000,000 (Direct Cost: ¥11,000,000); Fiscal Year 2007: ¥11,000,000 (Direct Cost: ¥11,000,000); Fiscal Year 2006: ¥11,000,000 (Direct Cost: ¥11,000,000); Fiscal Year 2005: ¥11,300,000 (Direct Cost: ¥11,300,000)
• Keywords: シグナル伝達と遺伝子発現 / 膜型増殖因子 / shedding / CTFシグナル / 転写リプレッサー / レトログレード小胞輸送 / HB-EGF / HB-EGF-CTF / repressor / BCL6 / c-myc / PLZF / Bcl6 / 増殖因子 / 細胞増殖 / Shedding / Transcriptional repressor / Pbx 1 / 小胞輸送 / 細胞増殖抑制

Research Abstract

We analyzed the function of C-terminal fragment (CTF) signals which are evoked by the shedding of a representative membrane-anchored growth factor proHB-EGF. We found that (1) the CTF of proHB-EGF was internalized into cytosol by endocytosis and localized at the innernuclear membrane by retrograde vesicle transport, (2) the CTF regulated several gene expression essential for cell growth promotion by interacting with and regulating gene repressors, and (3) the CTF signal was constitutively active in some tumor cell lines.

Research Products

• [Journal Article] Induction of striatal neurogenesis and generation of region-specific functional mature neurons after ischemia by growth factors. (2010)
  • Author(s): Yoshikawa G, Momiyama T, Oya S, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N.
  • Journal Title: J Neurosurg. (In press)
  • Peer Reviewed
• [Journal Article] Novel monoclonal antibodies recognizing the active conformation of epidermal growth factor receptor. (2010)
  • Author(s): Ise N, Omi K, Miwa K, Honda H, Higashiyama S, Goishi K.
  • Journal Title: Biochem Biophys Res Commun. (In press)
  • Peer Reviewed
• [Journal Article] Activation of epidermal growth factor receptor gene is involved in transforming growth factor-beta-mediated fibronectin expression in a chondrocyte progenitor cell line. (2010)
  • Author(s): Takeda H, Inoue H, Kutsuna T, Matsushita N, Takahashi T, Watanabe S, Higashiyama S, Yamamoto H.
  • Journal Title: Int J Mol Med. (In press)
  • Peer Reviewed
• [Journal Article] Insulin-Induced Ectodomain Shedding of Heparin-Binding Epidermal Growth Factor-Like Growth Factor in Adipocytes In Vitro. (2010)
  • Author(s): Yamamoto T, Suganami T, Kiso-Narita M, Scherle PA, Kamei Y, Isobe M, Higashiyama S, Ogawa Y.
  • Journal Title: Obesity (In press)
  • Peer Reviewed
• [Journal Article] Mitochondrial reactive oxygen species mediate GPCR-induced TACE/ADAM17-dependent transforming growth factor-alpha shedding. (2009)
  • Author(s): Myers TJ, Higashiyama S
  • Journal Title: Mol Biol Cell. 20(24) Pages: 5236-49
• [Journal Article] Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice. (2009)
  • Author(s): Oyagi A, Higashiyama S
  • Journal Title: PLoS One. 4(10)
• [Journal Article] Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. (2009)
  • Author(s): Xu D, Higashiyama S
  • Journal Title: Immunity 30(6) Pages: 802-16
• [Journal Article] Insufficiency of pro-heparin-binding epidermal growth factor-like growth factor shedding enhances hypoxic cell death in H9c2 cardiomyoblasts via the activation of caspase-3 and c-Jun N-terminal kinase. (2009)
  • Author(s): Uetani T, Inoue H, Higashiyama S
  • Journal Title: J Biol Chem. 284(18) Pages: 12399-409
• [Journal Article] Mitochondrial reactive oxygen species mediate GPCR-induced TACE/ADAM17-dependent transforming growth factor-alpha shedding. (2009)
  • Author(s): Myers TJ, Brennaman LH, Stevenson M, Higashiyama S, Russell WE, Lee DC, Sunnarborg SW
  • Journal Title: Mol Biol Cell. 24 Pages: 5236-5249
  • Peer Reviewed
• [Journal Article] Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice. (2009)
  • Author(s): Oyagi A, Oida Y, Kakefuda K, Shimazawa M, Shioda N, Moriguchi S, Kitaichi K, Nanba D, Yamaguchi K, Furuta Y, Fukunaga K, Higashiyama S, Hara H
  • Journal Title: PLoS One 10
  • Peer Reviewed
• [Journal Article] Thromboxane A2 receptor-mediated epidermal growth factor receptor transactivation : involvement of PKC-delta and PKC-epsilon in the shedding of epidermal growth factor receptor ligands. (2009)
  • Author(s): Uchiyama K, Saito M, Sasaki M, Obara Y, Higashiyama S, Nakahata N
  • Journal Title: Eur J Pharm Sci. 38 Pages: 504-511
  • Peer Reviewed
• [Journal Article] Localisation of endothelin B receptor variants to plasma membrane microdomains and its effects on downstream signalling. (2009)
  • Author(s): Grossmann S, Higashiyama S, Oksche A, Schaefer M, Tannert A
  • Journal Title: Mol Membr Biol. 5 Pages: 279-792
  • Peer Reviewed
• [Journal Article] Serine protease inhibitor Kazal type 1 promotes proliferation of pancreatic cancer cells through the epidermal growth factor receptor. (2009)
  • Author(s): Ozaki N, Ohmuraya M, Hirota M, Ida S, Wang J, Takamori H, Higashiyama S, Baba H, Yamamura K.
  • Journal Title: Mol Cancer Res 9 Pages: 1572-1581
  • Peer Reviewed
• [Journal Article] Carbon-ion beam irradiation effectively suppresses migration and invasion of human non-small-cell lung cancer cells. (2009)
  • Author(s): Akino Y, Teshima T, Kihara A, Kodera-Suzumoto Y, Inaoka M, Higashiyama S, Furusawa Y, Matsuura N
  • Journal Title: Int J Radiat Oncol Biol Phys. 75 Pages: 475-481
  • Peer Reviewed
• [Journal Article] Ectodomain shedding of E-cadherin and c-Met is induced by Helicobacter pylori infection. (2009)
  • Author(s): Schirrmeister W, Gnad T, Wex T, Higashiyama S, Wolke C, Iaumann M, Lendeckel U.
  • Journal Title: Exp Cell Res. 315 Pages: 3500-3508
  • Peer Reviewed
• [Journal Article] Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. (2009)
  • Author(s): Xu D, Holko M, Sadler AJ, Scott B, Higashiyama S, Berkofsky-Fessler W, McConnell MJ, Pandolfi PP, Licht JD, Williams BR
  • Journal Title: Immunity. 30 Pages: 802-816
  • Peer Reviewed
• [Journal Article] BCL6 degradation caused by the interaction with the C-terminus of pro-HB-EGF induces cyclin D2 expression in gastric cancers. (2009)
  • Author(s): Hirata Y, Ogasawara N, Sasaki M, Mizushima T, Shimura T, Mizoshita T, Mori Y, Kubota E, Wada T, Tanida S, Kataoka H, Kamiya T, Higashiyama S, Joh T
  • Journal Title: Br J Cancer. 100 Pages: 1320-1329
  • Peer Reviewed
• [Journal Article] Insufficiency of pro-heparin-binding epidermal growth factor-like growth factor shedding enhances hypoxic cell death in H9c2 cardiomyoblasts via the activation of caspase-3 and c-Jun N-terminal kinase. (2009)
  • Author(s): Uetani T, Nakayama H, Okayama H, Okura T, Higaki J, Inoue H, Higashiyama S.
  • Journal Title: J Biol Chem. 284 Pages: 12399-12409
  • Peer Reviewed
• [Journal Article] Attenuation of Notch signaling promotes the differentiation of neural progenitors into neurons in the hippocampal CA1 region after ischemic injury. (2009)
  • Author(s): Oya S, Yoshikawa G, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N.
  • Journal Title: Neuroscience. 58 Pages: 683-692
  • Peer Reviewed
• [Journal Article] Attenuation of Notch signaling promotes the differention of neural progenitois in the hippocampal CAI region after ischemic injury (2009)
  • Author(s): Oya, S., et.al.
  • Journal Title: Neumscience 158 Pages: 683-692
  • Peer Reviewed
• [Journal Article] Insufficient shedding ofproHB-EGF enhances hypoxic cell death in H9c2 caxdiomyoblasts via activation of Caspase-3 and c-Jun N-terminal kinase (2009)
  • Author(s): Uetani, T., et.al.
  • Journal Title: J.Biol Chem (in press)
  • Peer Reviewed
• [Journal Article] BCL6 degradation caused by the interaction with the C-terminus of pro-HB-EGF induces cyclin D2 expression in gastric cancers (2009)
  • Author(s): Hirata, Y., et.al.
  • Journal Title: Br J Gancer (in press)
  • Peer Reviewed
• [Journal Article] Plasma-membrane-anchored growth factor pro-amphiregulin binds A-type lamin and regulates global transcription. (2008)
  • Author(s): Isokane M, Hieda M, Higashiyama S
  • Journal Title: J Cell Sci. 121(Pt21) Pages: 3608-18
• [Journal Article] Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane. (2008)
  • Author(s): Hieda M, Higashiyama S
  • Journal Title: J Cell Biol. 180(4) Pages: 763-9
• [Journal Article] Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands. (2008)
  • Author(s): Higashiyama S
  • Journal Title: Cancer Sci 99(2) Pages: 214-20
  • NAID: 10024001752
• [Journal Article] An intermediary role of proHB-EGF shedding in growth factor-induced c-Myc gene expression. (2008)
  • Author(s): Nanba D, Inoue H, Higashiyama S
  • Journal Title: J Cell Physiol. 214(2) Pages: 465-73
• [Journal Article] Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia (2008)
  • Author(s): Oya, S., et al.
  • Journal Title: Neurreepart 19 Pages: 805-809
  • Peer Reviewed
• [Journal Article] Membrane-anchored growlh factor amphiregulin on cell surface targets tothe inner nuclear membrane (2008)
  • Author(s): lsokane, M., et.al.
  • Journal Title: J. Cell Sci 121 Pages: 3608-3618
  • Peer Reviewed
• [Journal Article] Membrane-anchored growth factor HB-EGF on cell surface targets to the inner nuclear memberane. (2008)
  • Author(s): Hieda, M., et. al.
  • Journal Title: J. Cell Biol. 180 Pages: 763-769
  • Peer Reviewed
• [Journal Article] he carboxyl-terminal fragment of pro-HB-EGF reverses Bcl6-mediated gene repression. (2007)
  • Author(s): Kinugasa Y, Hieda M, Hori M, Higashiyama S
  • Journal Title: J Biol Chem. 282(20) Pages: 14797-806
• [Journal Article] Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression. (2007)
  • Author(s): Shiraishi K, Inoue H, Higashiyama S
  • Journal Title: Oncogene 26(3) Pages: 339-48
• [Journal Article] An intermediary role of proHB-EGF shedding in growth factor-induced c-myc expression (2007)
  • Author(s): Nanba, D., et. al.
  • Journal Title: J.Cell. Physiol. 214 Pages: 465-473
  • Peer Reviewed
• [Journal Article] Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts. (2007)
  • Author(s): Furochi, H., et. al.
  • Journal Title: FEBS Lett. 581 Pages: 5743-5750
  • Peer Reviewed
• [Journal Article] Human comeal epithelial cell proliferation by epiregulin and its cross-induction by other EGF family members. (2007)
  • Author(s): Morita, S., et. al.
  • Journal Title: Molecular Vision 13 Pages: 2119-2128
  • Peer Reviewed
• [Journal Article] Evidence against roles for phorbol binding protein Muncl13-3, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer Alzheimer APP ectodomain shedding. (2007)
  • Author(s): Ikin, A.F., et. al.
  • Journal Title: Molecular Neurodegeneration 2 Pages: 23-23
  • Peer Reviewed
• [Journal Article] Pbx1 is a major target of PLZF-mediated melanoma cell growth suppression. (2007)
  • Author(s): Shiraishi, K., Yamasaki, K., Nanba, D., Inoue, H., Hanakawa, Y., Shirakata, Y., Hashimoto, K., Higashiyama, S.
  • Journal Title: Oncogene 26 Pages: 339-348
• [Journal Article] The carboxy-terminal fragment of proHB-EGF reverses Bcl6-mediated gene expression. (2007)
  • Author(s): Kinugasa, Y., Hieda, M., Hori, M., Higashiyama, S.
  • Journal Title: J. Biol. Chem. (in press)
• [Journal Article] PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation. (2006)
  • Author(s): Kikugawa, T., Kinugasa, Y., Shiraishi, K., Nanba, D., Nakashiro K., Tanji, N., Yokoyama, M., Higashiyama, S.
  • Journal Title: The Prostate 66 Pages: 1092-2099
• [Journal Article] Activity-dependent shedding of heparin-binding EGF-like growth factor in brain neurons. (2006)
  • Author(s): Shishido, Y., Tanaka, T., Piao, Y.S., Araki, K., Takei, N., Higashiyama, S., Nawa H.
  • Journal Title: Biochem Biophys Res Commun. 348 Pages: 963-970
• [Journal Article] Loss of HB-EGF in smooth muscle or endothelial cell lineages causes heart valve malformation and cardiac hypertrophy. (2006)
  • Author(s): Nanba, D., Kinugasa, Y., Morimoto, C., Koizumi, M., Yamamutra, H., Takahashi, K., Takakura, N., Mekada, E., Hashimoto, K., Higashiyama, S.
  • Journal Title: Biochem Biophys Res Commun. 350 Pages: 315-321
• [Journal Article] Ectodomain shedding of membrane-anchored heparin-binding EGF like growthfactor and subcellular localization of the C-terminal fragment in a cell cycle (2005)
  • Author(s): Toki, F. et al.
  • Journal Title: J. Cell. Physiol. 202 Pages: 839-848
• [Journal Article] Heparin-binding EGF-like growth factor is essential for keratinocyte migration in skin wound heaking (2005)
  • Author(s): Shirakata, Y. et al.
  • Journal Title: J. Cell Science 118 Pages: 2363-2370
• [Journal Article] G protein coupling and second messenger generation are indispensable for metalloprotease-dependent, heparin-binding epidermal growth factor shedding through angiotensin II type-1 receptor. (2005)
  • Author(s): Mifune, M.et al.
  • Journal Title: J. Biol. Chem 280 Pages: 26592-26599
• [Journal Article] Induction of Keratinocyte Migration via Transactivation of the Epidermal Growth Factor Receptor by the Antimicrobial Peptide LL-37. (2005)
  • Author(s): Tokumaru, S. et al.
  • Journal Title: J. Immunol. 175 Pages: 4662-4668
• [Journal Article] Alternative recycling of E-cadeherin depends on metalloprotease activity of ADAM9 (2005)
  • Author(s): Hirao, F. et al.
  • Journal Title: Exp. Cell Res. 12 Pages: 331-339
• [Journal Article] The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation. (2005)
  • Author(s): Fukui, K., et al.
  • Journal Title: Cell Metabolism 2 Pages: 373-384
• [Presentation] 膜型増殖因子のEctodomain Shedding-分子機構から生理機能まで (2009)
  • Author(s): 東山繁樹
  • Organizer: 第73回 日本生化学会中部支部例会シンポジウム
  • Place of Presentation: 名古屋市立大学
  • Year and Date: 2009-05-23
• [Presentation] Nuclear signaling of membrane-anchored growth factors and cell growth regulation (Invited) (2009)
  • Author(s): Shigeki Higashiyama
  • Organizer: International Symposium "New Frontiers in Cancer Research"
  • Place of Presentation: The Hokkaido University Conference Hall (北海道)
  • Year and Date: 2009-03-18
• [Presentation] Inner nuclear membrane targeting of membrane-anchored growth factors and transcriptional regulation (Invited). (2009)
  • Author(s): Shigeki Higashiyama
  • Organizer: Gordon Research Conference "Signal Transduction within the Nucleus"
  • Place of Presentation: Ventura, CA, USA
• [Presentation] A zinc finger transcription factor regulates vascular sprouting through the downregulation of Notch signaling in vascular endothelial cells. (2009)
  • Author(s): Hidetaka Ohnuki, Hirofumi Inoue, Hironao Nakayama, Shinji Fukuda, Shigeki Higashiyama
  • Organizer: Keystone Symposia -Angiogenesis and Lymphangiogenesis in Cancer-
  • Place of Presentation: Big Sky Resort, Big Sky, Montana, USA (Hidetaka Ohnuki received Keystone Symposia Scholarship Award, NIH, National Cancer Institute Grant #1R13CA135834-01. )
• [Presentation] Inner nuclear membrane translocation and nuclear signaling of membrane-anchored growth factors (2009)
  • Author(s): Shigeki Higashiyama
  • Organizer: 第61回日本細胞生物学会大会シンポジウム
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Inner nuclear membrane targeting of membrane-anchored growth factors and transcriptional regulation (2009)
  • Author(s): Shigeki Higashiyama
  • Organizer: Gordon Research Conference "Signal Transduction within the Nucleus"
  • Place of Presentation: Ventura, California, USA
• [Presentation] A zine finger transcnption factorregulates vascular sproutmg hough the down egulaion of Notch signaling in vascular endothelial cells (2009)
  • Author(s): Hidetaka Ohnuki, Shigeki Higashiyama, et.al.
  • Organizer: Keystone Symposia-Angiiogenesis and Lymphangiogenesis in Cancer-
  • Place of Presentation: Big Sky, MT, USA
• [Presentation] Inner nuclear membrane targetmg of membrane anchored growth factors and transcriptional regulation (Invited) (2009)
  • Author(s): Shigeki Higashiyama
  • Organizer: Gordon Research Conference Signal Transduction Within The Nucleus-
  • Place of Presentation: Ventura, CA, USA
• [Presentation] 膜型填殖因子amphiregulinの細胞内輪送経路およびその解析 (2008)
  • Author(s): 礒兼真由美、東山繁樹 (他2名)
  • Organizer: 第60回日本細胞生物学会大会
• [Presentation] 膜型増殖因子EGFファミリー分子は細胞膜から核膜へ局在変化する (2008)
  • Author(s): 檜枝美紀、東山繁樹(他1名)
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: パシフィコ横浜(横浜)
• [Presentation] Inner nuclear membrane targeting ofpro-amphiregulin regulates Oral Squamous Cell Carcinoma cell viability (2008)
  • Author(s): Mayumi Isokane, Shigeki Higashivama, et.al.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
• [Presentation] Inner nuclear membrane translocat ionandtranscriptionalxegulation of proHB-EGF and pro amphiregulin (International Session) (2008)
  • Author(s): Shigeki Higashryama
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議揚 (名古屋)
• [Presentation] Plasma membrane anchored growth factors proHB EGF and proamphiregulin targeted to the nuclear inner membrane and regulate gene expression (Symposaum) (2008)
  • Author(s): Shigeki Higasluyama, et.al.
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド (神戸)
• [Presentation] Ectodomian shedding ofEGF family members-the molecular mechanism and the physiological roles-(Symposium) (2008)
  • Author(s): Hirofulrn Inoue, Shigeki Higasluyama, et.al.
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイラント (神戸)
• [Presentation] The ectodomian shedding of amphregulm (AREG) is regulated by a 35kDa protem, a novel pmAREG associated protein (2008)
  • Author(s): Hixonao Nakayama, Shigeki Thgashiyama, et.al.
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸)
• [Presentation] Plasma membrane anchored growth factors HB EGF and amphmegulm targeted to the inner nuclear membrane and regulate gene expression (2008)
  • Author(s): Maynmi Isokane, Shigeki Higashiyama, et.al.
  • Organizer: Cold Spring Harbor Laboratory Meeting
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
• [Presentation] Sheddingフィールド形成因子同定と増殖因子シグナル制御機構 (2007)
  • Author(s): 中山寛尚、井上博文、東山繁樹
  • Organizer: 第30回日本分子生物学会 第80回日本生化学会大会 合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] 増殖因子切断による心筋細胞死誘導制御の解析 (2007)
  • Author(s): 上谷晃由、井上博文、大蔵隆文、檜垣實夫、東山繁樹
  • Organizer: 第30回日本分子生物学会 第80回日本生化学会大会 合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Membrane-anchored growth factor HB-EGF on cell surface targets to the nuclear membrane and regulates gene expression (2007)
  • Author(s): Miki Hieda and Shigeki Higashiyama
  • Organizer: 国際シンポジウム「メンブレントラフィック」
  • Place of Presentation: 淡路島
  • Year and Date: 2007-11-27
• [Presentation] Amphiregulin overexpressed in Oral Squamous Cell Carcinoma cell lines accumulates at the inner nuclear membrane. (2007)
  • Author(s): Mayumi Isokane, Shigeki Higashiyama, et. al.
  • Organizer: 第66回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Molecular target therapy for gastric cancer. suppression of proHb-EGF carboxy-terminal fragment nuclear translocation, (2007)
  • Author(s): Takaya Shimura, Shigeki Higashiyama, et. al.
  • Organizer: 第66回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] The carboxy-terminal fragment of proHB-EGF reverses Bc16-mediated gene expression. (2007)
  • Author(s): Yumi Kinugasa, Shigeki Higashiyama, et. al.
  • Organizer: 第66回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Membrane-anchored growth factor HB-EGF on cell surface targets to the nuclear membrane and regulates gene expression (2007)
  • Author(s): Miki Hieda and Shigeki Higashiyama
  • Organizer: EMBO Conference Series on Nuclear structure and Dynamics
  • Place of Presentation: Montpellier、France
  • Year and Date: 2007-09-04
• [Presentation] Membrane-anchored growth factor amphiregulin translocates to the inner nuclear membrane via retrograde membrane trafficking. (2007)
  • Author(s): Mayumi Isokane, Shigeki Higashiyama, et. al.
  • Organizer: EMBO Conference Series on Nuclear structure and Dynamics
  • Place of Presentation: Montpellier、France
  • Year and Date: 2007-09-04
• [Presentation] Membrane-anchored growth factor amphiregulin translocates to the inner nuclear memberane via retrograde membrane trafficking. (2007)
  • Author(s): Mayumi Isokane, Shigeki Higashiyama, etc.
  • Organizer: 第40回発生生物学会第59回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-06-01
• [Presentation] Membrane-anchored growth factor, HB-EGF targets to the nuclear membrane and regulates gene expression (2007)
  • Author(s): Miki Hieda, Shigeki Higashiyama, etc.
  • Organizer: 第40回発生生物学会第59回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-05-30
• [Presentation] Ectodomain shedding of membrane-anchored growth factor HB-EGF by ADAM and HB-EGF-C terminal fragment signaling. (2005)
  • Author(s): Shigeki Higahsiyama
  • Organizer: The Kennedy institute of Rheumatology Symposium, Metalloproteinases
  • Place of Presentation: Biology and Pathology, London, UK
• [Book] 細胞増殖因子と再生医療 (2006)
  • Author(s): 松本邦夫, 田畑泰彦, 東山繁樹 他
  • Total Pages: 401
  • Publisher: メディカルレビュー社
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/biochem2/index.html
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/biochem2/index.html
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/bioochem2/index.html
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/biochem2/index.html
• [Patent(Industrial Property Rights)] 新規ユビキチンリガーゼ及びその利用法 (2009)
  • Inventor(s): 東山繁樹, 井上博文, 大貫秀隆
  • Industrial Property Rights Holder: 国立大学法人愛媛大学
  • Filing Date: 2009-12-04
• [Patent(Industrial Property Rights)] 新規ユビキチンチガーゼ複合体及びその利用法 (2009)
  • Inventor(s): 東山繁樹、井上博文、大貫秀隆
  • Industrial Property Rights Holder: 愛媛大学
  • Industrial Property Number: 2009-277073
  • Filing Date: 2009-12-04
• [Patent(Industrial Property Rights)] 血管新生制御剤, 及びそのスクリーニング方法、並びにスクリーニング用キット (2008)
  • Inventor(s): 東山繁樹、井上博文、大貫秀隆
  • Industrial Property Rights Holder: 国立大学法人愛媛大学
  • Filing Date: 2008-08-14