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1996 Fiscal Year Final Research Report Summary

ELUCIDATION OF THE INTRACELLULAR CALCIUM SIGNAL TRANSDUCTION WITH THE MOLECULAR PHARMACOLOGICAL APPROARCH

Research Project

Project/Area Number 06404019
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionNAGOYA UNIVERSITY

Principal Investigator

HIDAKA Hiroyoshi  NAGOYA UNIVERSITY SCHOOL OF MEDICINE,PHATMACOLOGY,PROFESSOR, 医学部, 教授 (80100171)

Co-Investigator(Kenkyū-buntansha) YOKOKURA Hisayuki  NAGOYA UNIVERSITY SCHOOL OF MEDICINE,PHARMACOLOGY, ASSISTANT PROFESSOR, 医学部, 助手 (90273242)
WATANABE Yasuo  NAGOYA UNIVERSITY SCHOOL OF MEDICINE,PHARMACOLOGY, ASSISTANT PROFESSOR, 医学部, 助手 (10273228)
NIKI Ichiro  NAGOYA UNIVERSITY SCHOOL OF MEDICINE,PHARMACOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (10262908)
Project Period (FY) 1994 – 1996
KeywordsCALCIUM SIGNAL TRANSDUCTION / CALMODULIN / CALMODULIN-DEPENDENT PROTEIN KINASE / PROTEIN KINASE CASCADES
Research Abstract

Research on cellular signals, which depend heavily on physiological, biochemical and enzymatic studies, has made a rapid progress in the last 10 years with the break through introduction of such molecular biotogical approach as cDNA cloning. We studied molecular basis of the intracellular calcium signal transduction system by protein chemical, molecular biological, and molecular pharmacological approach. We have examined the mechanisms by which a novel Ca2+/calmodulin-dependent protein kinase V(CaM kinase V) was activated by phosphorylation. Physicochemical or biochemical properties of CaM kinase V were also analyzed Furthermore, polyclonal antibody against CaM kinase V was prepared and tissue distribution and immunohistochemical localization of CaM kinase V were studied. We have then discovered the CaM kinase V-activator which was necessary for CaM kinase V catalytic activity. Interestingly, the CaM kinase V-activator did phosphorylate Ca2+/calmodulin-dependent protein kinase IV(CaM kinase IV)associated with its activation. Finally, we suggested that there were new CaM kinase cascades such as those of MAP kinase. We have been studying to analyze biological function using synthesized molecule to activate or inhibit the activities of the target molecule. Based on these studies in creating designed molecular probes acting in the intracellular signal transduction, we have clarified the physiological functions of the CaM kinase which are closely linked to the intracellular signal transduction. Recently, we have cloned two new Ca2+/calmodulin-dependent protein kinase I(CaM kinase I) isoforms from rat brain and CaM kinase V has been thought to be an isoform of CaM kinase I.

  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] H.Ohta: "Identification and purification of Ca^<2+>/calmodulin-dependent protein kinase V from human gastric carcinoma." Biochim. Biophys. Acta.((in press))

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Yokokura: "Isolation and comparison of rat cDNAs encoding Ca^<2+>/calmodulin-dependent protein kinase I isoforms." Biochim. Biophys. Acta.((in press))

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] I.Niki: "Ca^<2+> signaling and intracellular Ca^<2+> binding proteins." J. Biochem. (review). 120・4. 685-698 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Hidaka: "KN-62: A specific Ca^<2+>/calmodulin inhibitor as a putative functional-seaching probe for intracellular signal transduction." Cardiovascular Drug Reviews. 14・1. 84-95 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.H.H.Win: "A new and potent calmodulin antagonist, HF-2035, Which inhibits vascular relaxation induced by nitric oxide synthase." Eur. J. Pharmacol.299. 119-126 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Kabir: "Regulation of preimplantation development of mouse embrvos: Effects of inhibition of myosin light-chain kinase, a Ca^<2+>/calmodulin-dependent enzyme." The Journal of Experimental Zoology. 274. 101-110 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.T.Lu: "Characterization of a calcium/calmodulin-dependent protein kinase homolog from maize roots showing light-regulated gravitropism." Planta.199. 18-24 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Nakamura: "Inhibition of P-glycoprotein multidrug resistance by an isoquinolinesulfonamide compound H-87 in rat ascites hepatoma AH66 cells." Biol. Pharm. Bull.19・6. 886-889 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Satoh: "Neuroprotecive properties of a protein kinase inhibitor against ischacmia-induced neuronal damage in rats and gerbils." Br. J. Pharmacol.118. 1592-1596 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Yokokura: "HMN-709, a chlorobenzenesulfonamide derivative and a new, membrane-permeable calmodulin antagonist." Jpn. J. Pharmacol.72. 127-135 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Hisatomi: "Ca^<2+>/calmodulin and cyclic 3,5'adenosine monophosphate control movement of secretory granules through protein phosphorylation/dephosphorylation in he pancreatic β-cell." Endocrinology. 137・11. 4644-4649 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Findik: "Protein kinase A inhibitors enhance radiation-induced apoptosis." J. Cell. Biochem. Biophys.57. 12-21 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Uemura: "A novel Ca^2/calmodulin-dependent protein kinase lacking autophosphorylation activity in the rabbit heart." Biochem. Biophys. Res. Commun.211・2. 562-569 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Yokokura: "The regulatory region of calcium/calmodulin-dependent protein kinase I contains closely associated autoinhibitory and calmodulin-binding domains." J. Biol. Chem.270・40. 23851-23859 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Inoue: "Purification and characterization of a novel protein activator of Ca^<2+>/calmodulin dependent protein kinase I." Biochem. Biophys. Res. Commun.215・3. 861-867 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.H.Obata: "Effect of KN-62, Ca^<2+>/calmodulin-dependent protein kinase II inhibitor, on adriamycin-resistance of human ovarian cancer cells." Biochem. Biophys. Res. Commun.215・2. 566-571 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Tokumitsu: "Activation mechanisms for Ca^<2+>/calmodulin-dependent protein kinase IV." J. Biol. Chem.269・46. 28640-28647 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Sugita: "Ca^<2+>/calmodulin-dependent protein kinase cascade." Biochem. Biophys.Res. Commun.203・1. 694-701 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Ito: "Ca^<2+>/calmodulin-dependent protein kinase V and I may form family of isoforms." Biochem. Biophys. Res. Commun.201・3. 1561-1566 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Ito: "Ca^<2+>/calmodulin-dependent protein kinase V: tissue distribution and immunohistochemical localization in rat brain." Arch. Biochem. Biophys.312・1. 278-284 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Hayashi: "Biphasic effect of estrogen on neuronal constitutive nitric oxide synthase via Ca^<2+>-calmodulin dependent mehcanizm." Biochem. Biophys. Res. Commun.203・2. 1013-1019 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Okazaki: "KN-62, a specific Ca^<2+>/calmodulin-dependent protein kinase inhibitor, reversibly depresses the rate of beating of cultured fetal mouse cardiac myocytes" J. Pharmacol. Exp. Ther.270・3. 1319-1324 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Minami: "The effect of KN-62, Ca^<2+>/calmodulin-dependent protein kinase II inhibitor on cell cycle." Biochem. Biophys. Res. Commun.199・1. 241-248 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Hidaka: "Molecular and cellular pharmacology of a calcium/calmodulin-dependent protein kinase II (CaM kinase II) inhibitor, KN-62, and proposal of CaM kinase phosphorylation cascades." Academic Press, San Diego, U.S.A., in Intracellular Signal Transduction, Advances in Pharmacology 36, 196-219 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 日高弘義: "キナーゼ阻害剤 「実験医学」別冊バイオマニュアルUPシリーズ "タンパク質の分子間相互作用実験法"" 羊土社, 186-193 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Hidaka: "Protein kinase inhibitors. in Essays in Biochemistry" Portland Press. London, U.K.,73-97 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Ohta: "Identification and purification of Ca^<2+>/calmodulin-dependent protein kinase V from human gastric carcinoma." Biochim.Biophys. Acta. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Yokokura: "Isolation and comparison of rat cDNAs encoding Ca^<2+>/calmodulin-dependent protein kinase I isoforms." Biochim.Biophys. Acta. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] I.Niki: "Ca^<2+> signaling and intracellular Ca^<2+> binding proteins." J.Biochem.(review). 120(4). 685-698 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Hidaka: "KN-62 : A specific Ca^<2+>/calmodulin inhibitor as a putative functional-seaching probe for intracellular signal transduction." Cardiovascular Drug Reviews. 14(1). 84-95 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.H.H.Win: "A new and potent calmodulin antagonist, HF-2035, which inhibits vascular relaxation induced by nitric oxide synthase." Eur.J.Pharmacol. 299. 119-126 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Kabir: "Regulation of preimplantation development of mouse embryos : Effects of inhibition of myosin light-chain kinase, a Ca^<2+>/calmodulin-dependent enzyme." The Journal of Experimental Zoology. 274. 101-110 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.-T.Lu: "Characterization of a calcium/calmodulin-dependent protein kinase homolog from maize roots showing light-regulated gravitropism." Planta. 199. 18-24 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Nakamura: "Inhibition of P-glycoprotein multidrug resistance by an isoquinolinesulfonamide compound H-87 in rat ascites hepatoma AH66 cells." Biol.Pharm.Bull.19(6). 886-889 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Satoh: "Neuroprotective properties of a protein kinase inhibitor against ischaemia-induced meuronal damage in rats and gerbils." Br.J.Pharmacol.118. 1592-1596 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Yokokura: "HMN-709, a chlorobenzenesulfonamide derivative and a new, membrane-permeable calmodulin antagonist." Jpn.J.Pharmacol.72. 127-135 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Hisatomi: "Ca^<2+>/calmodulin and cyclic 3,5' adenosine monophosphate control movement of secretory granules through protein phosphorylation/dephosphorylation in the pancreatic beta-cell." Endocrinology. 137(11). 4644-4649 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D.Findik: "Protein kinase A inhibitors enhance radiation-induced apoptosis." J.Cell.Biochem.57. 12-21 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Uemura: "A novel Ca^<2+>/calmodulin-dependent protein kinase lacking autophosphorylation activity in the rabbit heart." Biochem.Biophys.Res.Commun.211(2). 562-569 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Yokokura: "The regulatory region of calcium/calmodulin-dependent protein kinas I contains closely associated autoinhibitory and calmodulin-binding domains." J.Biol.Chem.270(40). 23851-23859 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Inoue: "Purification and characterization of a novel protein activator of Ca^<2+>/calmodulin dependent protein kinase I." Biochem.Biophys.Res.Commun.215(3). 861-867 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.H.Obata: "Effect of KN-62 Ca^<2+>/calmodulin-dependent protein kinase II inhibitor, on adriamycin-resistance of human ovarian cancer cells." Biochem.Biophys.Res.Commun.215(2). 566-571 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Tokumitsu: "Activation mechanisms for Ca^<2+>/calmodulin-dependent protein kinase IV." J.Biol. Chem.269(46). 28640-28647 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Sugita: "Ca^<2+>/calmodulin-dependent protein kinase cascade." Biochem.Biophys.Res.Commun.203(1). 694-701 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Ito: "Ca^<2+>/calmodulin-dependent protein kinase V and I mayform a family of isoforms." Biochem.Biophys.Res.Commun.201(3). 1561-1566 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Ito: "Ca^<2+>/calmodulin-dependent protein kinase V : tissue distribution and immunohistochemical localization in rat brain." Arch.Biochem.Biophys.312(1). 278-284 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Hayashi: "Biphasic effect of estrogen on neuronal constitutive nitric oxide synthase via Ca^<2+>-calmodulin-dependent mehcanizm." Biochem.Biophys.Res.Commun.203(2). 1013-1019 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Okazaki: "KN-62, a specific Ca^<2+>/calmodulin-dependent protein kinase inhibitor, reversibly depresses the rate of beating of cultured fetal mouse cardiac myocytes." J.Pharmacol.Exp.Ther.270(3). 1319-1324 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Minami: "The effect of KN-62, Ca^<2+>/calmodulin dependent protein kinase II inhibitor on cell cycle." Biochem.Biophys.Res.Commun.199(1). 241-248 (1994)

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

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Published: 1999-03-09  

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