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1998 Fiscal Year Final Research Report Summary

Manipulation of the interaction between protein kinase C and its specific substrate proteins

Research Project

Project/Area Number 09558088
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional biochemistry
Research InstitutionYokohama City University School of Medicine

Principal Investigator

OHNO Shigeo  Yokohama City Universisty School of Medicine, Department of Molecular Biology, Professor, 医学部, 教授 (10142027)

Co-Investigator(Kenkyū-buntansha) MIZUNO Keiko  Yokohama City Universisty School of Medicine, Department of Molecular Biology, A, 医学部, 助手 (90221803)
SUZUKI Atsushi  Yokohama City Universisty School of Medicine, Department of Molecular Biology, L, 医学部, 講師 (00264606)
Project Period (FY) 1997 – 1998
KeywordsHB-EGF / PKC / protein kinase C / ADAM / metaloprotease / shedding / extracellular domain / membrane proteins
Research Abstract

Protein kinase C (PKC) has been implicated in a variety of cellular responses that include cell growth, differentiation, and apoptosis, as well as responses to a variety of physiological signals and artificial stresses. Thus, it is very important to manipulate the function of PKC in a specific manner for pharmacological manipulation of the cellular signaling cascades as well as basic research for the understanding of the intracellular signaling network. In the present study, we searched for specific binding proteins for several isotypes of the PKC family and examined the physiological meaning the the molecular interaction through a variety of methods. MDC9 is a family of membrane anchored metaloproteases. Through the interaction cloning of PKC delta, we identified MDC9 as a specific binding protein and substrate for PKCdelata. PKCdelata binds to the 25 aa sequence of the cytoplasmic domain of MDC9 and phosphorylates it efficiently. Transfection experiments using activated and trans-dominant negative mutants of PKCdelata revealed that PKC delta is involved in the TPA-induced shedding of a membrane-anchored growth factor, HB-EGF.Similar analysis using MDC9 also revealed that MDC) is also involved in the TPA-induced shedding of HB-EGF.These results suggested that PKCdelata and MDC9 are involved in the TPA-induced shedding of HB-EGF and the direct molecular interaction between PKC delta and MDC9 is involved in this process. Since the signal-induced shedding of the extra-cellular domains of a variety of proteins plays a key role in a variety of developmental and physiological processes, the present finding opened the way for the understanding of the molecular mechanism of this quite importance processes.

  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Izumi, Y., Hirata, M., Hasuwa, H., Iwamoto, R., Umata, T., Miyado, K., Tamai, Y., Kurisaki, T., Sehara-Fujisawa, A., Ohno, S.and Mekada, E.: "A metalloprotease-disintegrin, MDC9/Meltrin-g/ADAM9, and PKCd and involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor." ENBOJ.24. 7260-7272 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kotani, K., Ogawa, W., Matsumoto, M., Kitamura, T., Sakaue, H., Hino, Y., Miyake, K., Sano, W., Akimoto, K., Ohno, S. and Kasuga M.: "Requirement of atypical PKCl for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes." Molecular and Cellular Biol.18. 6971-6982 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi, Y., Hirose, T., Tamai, Y., Hirai, S-I., Nagashima, Y., Fujimoto, T., Tabuse, Y., Kemphues, K.J.and Ohno, S. :"An atypical PKC directly associates and co-localizes at the epithelial tight junction with ASIP, a mammalian homologue of C.elegans polarity protein PAR-3." J.Cell Biol.143. 95-106 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akimoto, K., Nakaya, M., Yamanaka, T., Tanaka, J., Matsuda, S., Weng, Q-P., Avruch, J.and Ohno, S.: "Atypical PKCl binds and regulates p70 S6 kinase." Biochem.J.335. 417-424 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tabuse, Y., Izumi, Y., Piano, F., Kemphues, K.J., Miwa, J.and Ohno, S.: "Atypical Protein Kinase C Cooperates with PAR-3 to Establish Embryonic Polarity in Caenorhabditis elegans." Development. 125. 3607-3614 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokozeki, T., Homma, K, Kuroda, S., Kikkawa, U., Ohno, S., Takahashi, M., Imahori, K.and Kanaho, Y.: "Phosphatidic acid-dependent phosphorylation of a 29-kDa protein by protein kinase Calpha in bovine brain cytosol." J Neurochem. 71. 410-417 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oka, N., Yamamoto, M., Schwencke, C., Kawabe, J-I., Ebina, T., Ohno, S., Couet, J., Lisanti, M.P.and Ishikawa, Y.: "Caveolin interaction with protein kinase C." J.Biol.Chem.272. 33416-33421 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuno, K., Noda, K., Araki, T., Imaoka, T., Kobayashi, Y., Akita, Y., Shimonaka, M., Kishi, S.and Ohno, S.: "The proteolytic cleavage of protein kinase C isotypes, which generates kinase and regulatory fragments, Correlates with Fas-mediated and 12-0-tetradecanoyl-phorbol-13-acetate-induced apotosis." Eur.J., Biochem.250. 7-18 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lu, Z., Hornia, A., Jiang, Y-W., Frankel, P., Zang Q., Ohno, S.and Foster, D. A.: "Tumor-promotion by depleting cells of protein kinase Cd." Molecular and Cellular Biol.17. 3418-3428 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukumoto, S., Nishizawa, Y., Hosoi, M., Koyama, H., Yamakawa, K., Ohno, S.and Morii, H.: "Protein Kinase C delta isoform inhibits the proliferation of vascular smooth muscle cells through suppressing C1 cyclins expression." J.Biol.Chem.272. 13816-13822 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi, Y., Hirai, S., Tamai, Y., Fujise-Matsuoka, A., Nishimura, Y.and Ohno, S.: "A protein kinase C delta-binding protein SRBC whose expression is induced by serum starvation." J.Biol.Chem. 272. 7381-7389 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohno, S.: "The distinct biological potential of PKC isotypes." Protein Kinase C. 75-93 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大野茂男: "プロテインキナーゼCの構造生物学" タンパク質核酸酵素 増刊“構造生物学のフロンティア". 44. 404-411 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大野茂男: "プロテインキナーゼC" 実験医学、増刊 シグナル伝達研究の新しい局面. 16. 1736-1741 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西岡直也、大野茂男: "バソプレッシン受容体、受容体1997、" 生体の科学. 48. 417-419 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平井秀一: "PKC経路活性化と転写制御" 放射線生物研究. 32. 14-30 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大野茂男: "プロテインキナーゼC" 医学の歩み. 181. 836-837 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木厚、大野茂男: "脳・神経機能とプロテインキナーゼC" 蛋白質核酸酵素. 42. 411-417 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi, Y., Hirata, M., Hasuwa, H., Iwamoto, R., Umata, T., Miyado, K., Tamai, Y., Kurisaki, T., Sehara-Fujisawa, A., Ohno, S.and Mekada, E: "A metalloprotease-disintegrin, MDC9/Meltrin-g/ADAM9, and PKCd are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor." EMBO J. 24. 7260-7272 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kotani, K., Ogawa, W., Matsumoto, M., Kitamura, T., Sakaue, H., Hino, Y., Miyake, K., Sano, W., Akimoto, K., Ohno, S.and Kasuga M.: "Requirement of atypical PKC1 for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes." Molecular and Cellular Biol.18. 6971-6982 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi, Y., Hirose, T., Tamai, Y., Hirai, S-I., Nagashima, Y., Fujimoto, T., Tabuse, Y., Kemphues, K.J.and Ohno, S.: "An atypical PKC directly associates and co-localizes at the epithelial tight junction with ASIP, a mammalian homologue of C.elegans polarity protein PAR-3." J.Cell Biol.143. 95-106 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akimoto, K., Nakaya, M., Yamanaka, T., Tanaka, J., Matsuda, S., Weng, Q-P., Avruch, J.and Ohno, S.: "Atypical PKC1 binds and regulates p70 S6 kinase." Biochem.J.335. 417-424 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tabuse, Y., Izumi, Y., Piano, F., Kemphues, K.J., Miwa, J.and Ohno, S.: "Atypical Protein Kinase C Cooperates with PAR-3 to Establish Embryonic Polarity in Caenorhabditis elegans." Development. 125. 3607-3614 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokozeki, T., Homma, K., Kuroda, S., Kikkawa, U., Ohno, S., Takahashi, M., Imahori, K.and Kanaho, Y.: "Phosphatidic acid-dependent phosphorylation of a 29-kDa protein by protein kinase Calpha in bovine brain cytosol." J Neurochem Jul. 71 (1). 410-417 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oka N., Yamamoto, M., Schwencke, C., Kawabe, J-I., Ebina, T., Ohno, S., P.and Ishikawa, Y.: "Caveolin interaction with protein kinase C." J.Biol.Chem., Couet, J., Lisanti, M.272. 33416-33421 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizuno, K., Noda, K., Araki, T., Imaoka, T., Kobayashi, Y., Akita, Y., Shimonaka, M., Kishi, S.and Ohno, S.: "The proteolytic cleavage of protein kinase C isotyper, which generates kinase and regulatory fragments, correlates with Fas-mediated and 12-0-tetradecanoyl-phorbol-13-acetate-induced apotosis." Eur.J., Biochem.250. 7-18 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lu, Z., Hornia, A., Jiang, Y-W., Frankel, P., Zang Q., Ohno, S.and D.A.: "Tumor-promotion by depleting cells of protein kinase Cd." Molecular and Cellular Biol., Foster. 17. 3418-3428 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukumoto, S., Nishizawa, Y., Hosoi, M., Koyama, H., Yamakawa, K.: "Protein kinase C delta isoform inhibits the proliferation of vascular smooth muscle cells through suppressiong G1 cyclins expression." J.Biol.Chem., Ohno, S.and Morii, H.272. 13816-13822 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi, Y., Hirai, S., Tamai, Y., Fujise-Matsuoka, A., Nishimura, Y.and Ohno, S.: "A protein kinase C delta-binding protein SRBC whose expression is induced by serum starvation." J.Biol.Chem.272. 7381-7389 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohno, S.: "The distinct biological potential of PKC isotypes." in Protein Kinase C, pp75-93 (eds.Parker, P.J.and Dekker, L.V., R.G.Lands Company, Springer). (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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