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Intra-cellular signaling cascades involved in cellular stress responses

Research Project

Project/Area Number 09470034
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionYokohama City University School of Medicine

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) HIRAI Syu-ichi  Yokohama City University School of Medicine, Department of Molecular Biology, As, 医学部, 助教授 (80228759)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1998: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1997: ¥6,900,000 (Direct Cost: ¥6,900,000)
Keywordsstress response / JNK / MAP kinase / mRNA induction / binding protein / stabilization
Research Abstract

Previous work in our laboratory revealed the importance of a family of protein kinases, MUK/MLK family, as activators of JNK signaling cascade. In the present study, we first clearly shown that these protein kinases are the kinases that directly phosphorylates and activates the JNK activators, MKK7 and SEK1. Furthermore, we found that the mode of the activation of the JNK pathway through this family of protein kinases is unique in that the steady state levels of mRNAs for MUK and MST are regulated under cellular stress conditions. This raises the possibility that the activation of JNK pathway might involve the regulation of the amount of mRNA and/or protein of MUK/MST family protein kinases. In addition to such unique regulation, there is a protein, MIPP, which directly binds to MUK and destabilizes MUK.Further, there is a protein, 3-3, which binds to MUK and activates its ability to activate JNK pathway. Further studies of the mode of activation of JNK through MUK/MLK family of protein kinases is required for clarification of the physiological importance of this unique family of protein kinases in cellular stress responses.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (45 results)

All Other

All Publications (45 results)

  • [Publications] Hirai, S-I., Noda, K., Moriguchi, T., nishida, E., Yamashita, A., Deyama, T., Fukuyama, K.and Ohno, S.: "Differential activation of two JNK activators, MKK7 and SEKI, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2." J.Biol.Chem.273. 7406-7412 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yuasa, T., Ohno, S., Kehrl, J.H.and Kyriakis, J.M.: "Tumor necrosis factor signaling to stress-activated protein kinase (SAPK) /Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase I and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and P38." J.Biol.Chem.273. 22681-22692 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nyui, N., Tamura, K., Mizuno, K., Ishigami, T., Kihara, M., Ochiai, H., Kimura, K., Umemura, S., Ohno, S., Taga, T.and Ishii, M.: "gp130 is involved in stretch-induced MAP kinase activation in cardiac myocytes." Biochem.Biophys.Res.Commun.245. 928-932 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhuang, S., Hirai, S-I, Mizuno, K., Suzuki, A., Akimoto, K., Izumi, Y., Yamashita, A.and Ohno, S.: "Involvement of protein kinase C in the activation of extracelluar signal-regulated kinase 1/2 by UVC irradiation." Biochem.Biophys.Res.Commun.240. 273-278 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osada, S., Izawa, M., Saito, R., Mizuno, K., Suzuki, A., Hirai, S.and Ohno. S.: "YSKI, a novel mammalian protein kinase structurally related to Ste20 and SPSI, but not involved in the known MAPK pathways." Oncogene. 14. 2047-2057 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirai, S., Katoh, M., Terada, M., Kyriakis, J.M., Zon, L.I., Avruch, J. and Ohno, S.: "MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEKI, an activator of JNK/SAPK." J.Biol.Chem.272. 15167-15173 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueda, Y., Hirai, S., Osada, S., Suzuki, A., Mizuno, K. and Ohno, S.: "Protein kinase Cd activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf." J.Biol.Chem.271. 23512-23519 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Rana, A., Gallo, K., Godowski, P., Hirai, S., Ohno, S., Zon, L., Kyriakis, J.M.and Auruch, J.: "The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1." J.Biol.Chem.271. 19025-19028 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirano, M., Osada, S., Aoki, T., Hirai, S., Hosaka, M., Inoue, J., and Ohno, S.: "MEK kinase is involved in TNFa-mediated activation of NFkB and degradation of IkBa." J.Biol.Chem.271. 13234-13238 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirai, S., Izawa, N.,Osada, S., Spyrou, G.and Ohno, S.: "Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK." Oncogene. 12. 641-650 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 平井秀一、大野茂男: "MUKによるJNK経路活性化" 生体の科学. 48. 130-135 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 平井秀一: "転写因子とシグナル伝達" 臨床医. 23. 717-720 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirai, S-I., Noda, K., Moriguchi, T., Nishida, E., Yamashita, A., Deyama, T., Fukuyama, K.and Ohno, S.: "Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2." J.Biol.Chem.273 (13). 7406-7412 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yuasa, T., Ohno, S., Kehrl, J.H.and Kyriakis, J.M.: "Tumor necrosis stress-activated protein kinase (SAPK) /Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38." J.Biol.chem., factor signaling to. 273. 22681-22692 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nyui, N., Tamura, K., Mizuno, K., Ishigami, T., Kihara, M., Ochiai, H., Kimura, K., Umemura, S., Ohno, S., Taga, T.and Ishii, M.: "gp130 is involved in stretch-induced MAP kinase activation in cardiac myocytes." Biochem. Biophys. Res.Commun.245 (3). 928-932 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhuang, S., Hirai, S-I, Mizuno, K., Suzuki, A., Akimoto, K., Izumi, Y., Yamashita, A.and Ohno, S.: "Involvement of protein kinase C in the activation of extracelluar signal-regulated kinase 1/2 by UVC irradiation." Biochem. Biophys. Res.Commun.240. 273-278 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osada, S., Izawa, M., Saito, R., Mizuno, K., Suzuki, A., Hirai, S.and Ohno.S.: "YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1, but not involved in the known MAPK pathways." Oncogene. 14. 2047-2057 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirai, S., Katoh, M., Terada, M., Kyriakis, J.M., Zon, L.I., Avruch, J.and: "MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of JNK/SAPK." J.Biol.Chem.Ohno, S.272. 15167-15173 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueda, Y., Hirai, S., Osaa, S., Suzuki, A., Mizuno K.and Ohno, S.: "activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf." J.Biol.Chem., Protein kinase Cd. 271. 23512-23519 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Rana, A., Gallo, K., Godowski, P., Hirai, S., Ohno, S., Zon, L., Kyriakis, J.M.and Auruch, J.: "The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1." J.Biol.Chem.271. 19025-19028 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirano, M., Osada, S., Aoki, T., Hirai, S., Hosaka, M., Inoue, J., and Ohno, S.: "involved in TNFa-mediated activation of NFKB and degradation of IkBa." J.Biol.Chem., MEK kinase is. 271. 13234-13238 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirai, S., Izawa, N., Osada, S., Spyrou, G.and Ohno, S.: "Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK." Oncogene. 12. 641-650 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirai,S-I.,Noda,K.,Moriguchi,T.,Nishida,E.,Yamashita,A.,Deyama,T.,Fukuyama,K.and Ohno,S.: "Differential activation of two JNK activators,MKK7 and SEK1,by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2." J.Biol.Chem.273. 7406-7412 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Zhuang,S.,Hirai,S-I,Mizuno,K.,Suzuki,A.,Akimoto,K.,Izumi,Y.,Yamashita,A.and Ohno,S.: "Involvement of protein kinase C in the activation of extracelluar signal-regulated kinase 1/2 by UVC irradiation." Biochem.Biophys.Res.Commun. 240. 273-278 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Osada,S.,Izawa,M.,Saito,R.,Mizuno,K.,Suzuki,A.,Hirai,S.and Ohno,S.: "YSK1,a novel mammalian protein kinase structurally related to Ste20 and SPS1,but not involved in the known MAPK pathways." Oncogene. 14. 2047-2057 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirai,S.,Katoh,M.,Terada,M.,Kyriakis,J.M.,Zon,L.L.,Avruch,J.and Ohno,S.: "MST/MLK2,a member of the mixed linage kinease family,directly phosphorylates and activates SEK1,an activator of JNK/SAPK." J.Biol.Chem.272. 15167-15173 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Osada,S.,Izawa,M.,Koyama,T.,Hirai,S.and Ohno,S.: "A domain containing the Cdc42/Rac interactive binding(CRIB)region of p65PAK inhibits transcriptional activation and cell transformation medited by the Ras-Rac pathway." FEBS Letter.404. 227-233 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirai,S.,Izawa,N.,Osada,S.,Spyrou,G.and Ohno,S.: "Activation of the JNK pathway by distantly related protein kinases,MEKK and MUK." Oncogene. 12. 641-650 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirai,S-I, Noda,K., Moriguchi,T., Nishida,E., Yamashita,A., Deyama,T., Fukuyama,K.and Ohno,S: "Differential activation of two JNK activators,MKK7 and SEK1,by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2" J.Biol.Chem.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki,A., Sugiyama,Y., Hayashi,Y., Nyui,N, Yoshida,M., Nonaka,I., Ishiura,S., Arahata,K.and Ohni,S.: "MKBP,a novel member of the small heat shock protein family,binds and activates the myotonic dystrophy protein kinase(DMPK)" J.Cell Biol.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Zhuang,S., Hirai,S-I, Mizuno,K., Suzuki,A., Akimoto,K., Izumi,Y., Yamashita,A., and Ohno,S.: "Incolvement of protein kinase C in the activation of extracelluar signal-regulated kinase 1/2 by UVC irradiation" Biochem.Biophys.Res.Commun. 240. 273-278 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ichimura,T., Ito,M., Itagaki,C., Takahashi,M., Horigome,T., Omata,S., Ohni,S.and Isobe,T.: "The 14-3-3 protein binds its target proteins with a common site losated towards the C-terminus" FEBS Letter. 413. 273-276 (1997)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nyui,N. Tamura,K., Mizuno,K., Ishigami,T., Hibi,K., Yabana,M., Kihara,M., Fukamizu,A., Ochiai,H., Umemura,S., Murakami,K., Ohno,S.and Ishii,M.: "Stretch-induced map kinase activation in cardiomyocytes of angiotensinogen-deficient mice" Biochem.Biophys.Res.Commun. 235. 36-41 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Osada,S., Izawa,M., Saito,R., Mizuno,K., Suzuki,A., Hirai,S.and Ohno.S.: "YSK1,a novel mammalian protein kinase structurally related to Ste20 and SPS1,but not involved in the known MAPK pathways" Oncogene. 14. 2047-2057 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kitamura,Y., Kitamura,T., Sakaue,H., Maede,T., Ueno,H., Nishio,S., Ohno,S., Osada,S., Sakaue,M., Ogawa,W.and Kasuga,M.: "Interaction of Nck-associated protein 1 with activated GTP-binding protein Rec." Biochem.J.322. 873-878 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ebina,T., Kawabe,J., Katada,T., Ohno,S., Homcy,C,J.and Ishikawa,Y.: "Conformation-dependentactivation of type II adenylylcyclase by protein kinase C." J.Cell Biochem. 64. 492-498 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Lu,Z., Homia,A., Jiang,Y-W., Frankel,P., Zang Q., Ohno,S.and Foster,D.A.: "Tumor-promotion by depleting cells of protein kinase Cδ." Molecular and Cellular Biol.17. 3418-3428 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukumoto,S., Nishizawa,Y., Hosoi,M., Koyama,H., Yamakawa,K., Ohno,S.and Morii,H.: "Protein kinase C delta iaofrom inhibits the proliferation of vascular smooth muscle cells through suppressiong G1 cyclins expression" J.Biol.Chem.272. 13816-13822 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirai,S., Katoh,M., Terada,M., Kyriakis,J.M., Zon,L.I., Avruch,J.and Ohno,S.: "MST/MLK2,a member of the mixed lineage kinase family,directly phosphorylates and activates SEK1,an activator of JNK/SAPK" J.Biol.Chem.272. 15167-15173 (1997)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] Osada,S., Izawa,M., Koyama,T., Hirai,S.and Ohno,S.: "A domain containing the Cdc42/Rac interactive binding(CRIB)region of p65PAK inhibits transcriptional activation and cell transformation mediated by the Ras-Rac pathway" FEBS Letter. 404. 227-233 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohno,S.: "The distinct biological potential of PKC isotypes" in Protein Kinase C. 75-93 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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