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Regulation of the activity of protein kinases depending on their functional domains

Research Project

Project/Area Number 07557200
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section試験
Research Field Pathological medical chemistry
Research InstitutionKobe University

Principal Investigator

KIKKAWA Ushio  Kobe University, Biosiganl Research Center, Professor, バイオシグナル研究センター, 教授 (40150354)

Co-Investigator(Kenkyū-buntansha) KONISHI Hiroaki  Kobe University, Biosiganl Research Center, Assistant, バイオシグナル研究センター, 助手 (40252811)
KURODA Shun-ichi  Kobe University, Biosiganl Research Center, Associate professor, バイオシグナル研究センター, 助教授 (60263406)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsfunctional domain / protein kinase / RAC-protein kinase / PH domain / protein kinase C / stress / phosphatidylinositol 3-kinase / regulation of activation / プロテインキナーゼ / 融合蛋白質 / 分子ファミリー / 蛋白質相互作用 / 免疫沈降法
Research Abstract

RAC-protein kinase (RAC-PK) and protein kinase C (PKC) have a catalytic domain highly homologous each other in the carboxyl-terminal regions, and the regulatory domain at their amino-terminal regions. RAC-PK and PKC have a PH domain and a Cl region, respectively, in the regulatory domain, and PKC has been shown to associate with PKC through the PH domain. We examined the regulation of these protein kinases through the regulatory domain in this study. In the initial study, the screening of the cDNA library was carried out and a novel clone of RAC-PK gamma was isolated in addition to the previously known RAC-PK alpha and beta. The PH domain of three types of RAC-PK associated with PKC subspecies in vitro. Analysis using deletion mutants revealed that the specific region for the binding with the PH domain was hardly identified in the PKC molecule, suggesting that the whole structure of PKC is important for the interaction with the PH domain. During the analysis of the measurement of RAC-PK activity expressed in cultured cell lines, it was revealed that RAC-PK is activated by cellular stress such as heat shock and hyperosmotic treatment. On the other hand, RAC-PK has been reported to be a downstream target of phosphatidylinositol 3-kinase, that is activated by the growth factor-stimulation. Activation of RAC-PK by cellular stress was, however, not suppressed by wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase. It is plausible that RAC-PK is activated through alternative pathways. Furthermore, the association of RAC-PK and PKC was enhanced by stress treatment. The mutual interaction between RAC-PK and PKC,probably through the protein-protein interaction, may have an important role in the intracellular signal transduction.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Konishi, H.: "Molecular cloning and characterization of a new member of the RAC protein kinase family: association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and βγ subunits of G proteins." Biochem. Biophys. Res. Commun.216. 526-534 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takanaga, H.: "Functional characterization of the promoter region of the mouse protein kinase Cγgene." FEBS Lett.368. 276-278 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kasahara, K.: "Distinct effects of saturated fatty acids on protein kinase C subspecies." J. Biochem.117. 648-653 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakamura, F.: "Characterization of Gq family. G proteins GL1α (G14α) , GL2α (G11α) , and Gqα expressed in the baculovirus-infected cell system." J. Biol. Chem.270. 6246-6253 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Igarashi, K.: "A novel phospholipid-binding peptide motif defined by an anti-idiotypic monoclonal antibody. Localization of phosphatidylserine-specitic binding sites on protein kinase C and phosphatidylserine decarboxylase." J. Biol. Chem.270. 29075-29078 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Oka, M.: "Differential down-regulation of protein kinase C subspecieds in normal human melanocytes: possible involvement of the ζ subspecies in growth regulation." J. Invest. Dermatol.105. 567-571 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Togawa, K.: "Ser-27, Tyr-10 and Tyr-7 in the α-chain of pig stomach H^+, K^+-ATPase as Ca^<2+>dependent phosphorylatable sites by intrinsic and extrinsic protein kinases" Biochem. Biophys. Res. Commun.227. 810-815 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuzaki, H.: "Isolation of the active form of RAC-protein kinase (PKB/Akt) from transfected COS-7 cells treated with heat shock stress and effects of phosphatidylinositol 3, 4, 5-trisphosphate and phosphatidylinositol 4, 5-bisphosphate on its enzyme activity" FEBS Lett.396. 305-308 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Haga, K.: "Phosphorylation of human ml muscarinic acetvlcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C" J. Biol. Chem.271. 2776-2782 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuroda, S.: "Protein-protein interaction of zine finger LIM domains with protein kinase C" J. Biol. Chem.271. 31029-31032 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Oka, M.: "Deletion of specific protein kinase C subspecies in human melanoma cells" J. Cell. Physiol.167. 406-412 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Konishi, H.: "Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase" Proc. Natl. Acad. Sci. USA. 93. 7639-7643 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Konishi, H., Kuroda, S., Tanaka, M., Matsuzaki, H., Ono, Y., Kameyama, K., Haga, T., and Kikkawa.U.: "Molecular cloning and characterization of a new member of the RAC protein kinase family : association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and betagamma subunits of G proteins." Biochem.Biophys.Res.Commun.216. 526-534 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takanaga, H., Mukai, H., Shimakawa, M., Konishi, H., Kikkawa, U., Koizumi, T., and Ono, Y.: "Functional characterization of the promoter region of the mouse protein kinase C g gene." FEBS Lett.368. 276-278 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kasahara, K., and Kikkawa, U.: "Distinct effects of saturaited fatty acids on protein kinase C subspecies." J.Biochem.117. 648-653 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakamura, F., Kato, M., Kameyama, K., Nukuda, T., Haga, T., Kato, H., Takenawa, T., and Kikkawa, U.: "Characterization of Gq family G proteins GL1alpha (G14alpha), GL2alpha (G11alpha), and Gqalpha expressed in the baculovirus-infected cell system." J.Biol.Chem.270. 6246-6253 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Igarashi, K., Kaneda, M., Yamaji, A., Saido, T.C., Kikkawa, U., Ono, Y., Inoue, K., and Umeda, M.: "A novel phospholipid-binding peptide motif defined by an antiidiotypic monoclonal antibody. Localization of phosphatidylserine-specific binding sites on protein kinase C and phosphatidylserine decarboxylase." J.Biol.Chem.270. 29075-29078 (1955)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Oka, M., Ogita, K., Ando, H., Kikkawa, U., and Ichihashi, M.: "Differential down-regulation of protein kinase C subspecies in normal human melanocytes : possible involvement of the zeta subspecies in growth regulation." J.Invest.Dermatol.105. 567-571 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Togawa, K., Kaya, S., Shimada, A., Imagawa, T., Taniguchi, K., Mardh, S., Corbin, J., Kikkawa, U., and Taniguchi, K.: "Ser-27, Tyr-10 and Tyr-7 in the a-chain of pig stomach H^+, K^+-ATPase as Ca^<2+> dependent phosphorylatable sites by intrinsic and extrinsic protein kinases." Biochem.Biophys.Res.Commun.227. 810-815 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuzaki, H., Konishi, H., Tanaka, M., Ono, Y., Takenawa, T., Watanabe, Y., Ozaki, S., Kuroda, S., and Kikkawa, U.: "Isolation of the active form of RAC-protein kinase (PKB/Akt) from transfected COS-7 cells treated with heat shock stress and effects of phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 4,5-bisphosphate on its enzyme activity." FEBS Lett.396. 305-308 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Haga, K., Kameyama, K., Haga, T., Kikkawa, U., Shiozaki, K., and Uchiyama, H.: "Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C." J.Biol.Chem.271. 2776-2782 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuroda, S., Tokunaga, C., Kiyohara, Y., Higuchi, O., Konishi, H., Mizuno, K., Gill, G.N., and Kikkawa, U.: "Protein-protein interaction of zinc finger LIM domains with protein kinase C." J.Biol.Chem.271. 31029-31032 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Oka, M., Ogita, K., Ando, H., Horikawa, T., Hayashibe, K., Saito, N., Kikkawa U., and Ichihashi, M.: "Deletion of specific protein kinase C subspecies in human melanoma cells." J.Cell.Physiol.167. 406-412 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Konishi, H., Matsuzaki, H., Tanaka, M., Ono, Y., Tokunaga, C., Kuroda, S., and Kikkawa, U.: "Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase." Proc.Natl.Acad.Sci.USA. 93. 7639-7643 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Togawa,K.: "Ser-27,Tyr-10 and Tyr-7 in the α-chain of pig stomach H^+,K^+-ATPase as Ca^<2+> dependent phosphorylatable sites by intrinsic and extrinsic protein kinases" Biochem.Biophys.Res.Commun.227. 810-815 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuzaki,H.: "Isolation of the active form of RAC-protein kinase(PKB/AKt)from transfected COS-7 cells treated with heat shock stress and effects of phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 4,5-bisphosphate on its enzyme activity" FEBS Lett.396. 305-308 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Haga,K.: "Phosphorylation of human ml muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C" J.Biol.Chem.271. 2776-2782 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kuroda,S.: "Protein-protein interaction of zine finger LIM domains with protein kinase C" J.Biol.Chem.271. 31029-31032 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oka,M.: "Deletion of specific protein kinase C subspecies in human melanoma cells" J.Cell.Physiol.167. 406-412 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Konishi,H.: "Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase" Proc.Natl.Acad.Sci.USA. 93. 7639-7643 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Konishi, H.: "Molecular cloning and characterization of a new member of the RAC protein kinase family : association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and βγ subunits of G proteins." Biochem. Biophys. Res. Commun.216. 526-534 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takanaga, H.: "Functional characterization of the promoter region of the mouse protein kinase Cγ gene." FEBS LCTT.368. 276-278 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kasahara, K.: "Distinct effects of satuvated fatty acidson prote in kinase C subspecies" J. Biochem.117. 648-653 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakamura, F.: "Characterization on Gq family G proteins GL1α (G14α),GL2α (G11α),and Gqα expressed in the baculovirus-infected cell system." J. Biochem.270. 6246-6253 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Igarashi, K.: "A novel phospholipid-binding peptide motif defined by and anti-idiotypic monoclonal antibody. Localization of phosphatidylsefine-specitic binding sites on protein kinase C and phosphatidylserme decarboxylase." J. Biol. Chem.270. 29075-29078 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Oka, M.: "Differential down-regulation of protein kinase C subspecies in normal human melanocytes : possible involvement of the ζ subspecies in growth regulation." J. Invest. Dermatol.105. 567-571 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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