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Regulation of inositol phospholipid-pelated 2nd messengers

Research Project

Project/Area Number 07044216
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionTohoku University

Principal Investigator

KONDO Hisatake  School of Medicine, Tohoku University, Professor, 医学部, 教授 (20004723)

Co-Investigator(Kenkyū-buntansha) VAN Blitters  オダンダ癌研究所, 生化学部門, 部長
GLOMSET John A  School of Medicine (Howard Hughes Med.Inst, ) University of Washington, 医学部, 教授
SAKAGAMI Hiroyuki  School of Medicine, Tohoku University, 医学部, 助手 (90261528)
GOTO Kaoru  School of Medicine, Tohoku University, 医学部, 助教授 (30234975)
KANOH Hideo  School of Medicine, Sapporo Medical University, 医学部, 教授 (70045475)
VAN BLITTERSWIJK Wim J  Het Netherlands Kanker Institute (The Nethderlands Cancer Institute)
BLITTERSWIJK ヴァン  オランダ癌研究所, 生化学部門, 部長
VON Blitlers  オランダ癌研究所, 生化学部門, 部長
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 1996: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1995: ¥5,800,000 (Direct Cost: ¥5,800,000)
KeywordsPI-turnover / DG-kinase / PA-phosphatase / gene cloning / arachidonic acid / molecular heterogeneity / PIキナーゼ / ホスファチジン酸ホスファターゼ / 遺伝子発現局在 / 脳 / 網膜 / ラット / ジアシルグリセロールキナーゼ / イノシトールリン脂質 / 核局在 / ショウジョウバエ
Research Abstract

Phosphoinositides (PI) turnover produces second messengers such as diacylglycerol (DG) and inositol triphosphate in response to external stimuli. DG acts as an activator of several forms of protein kinase C and is converted to phosphatidic acid (PA) by DG kinase. On the other hand, PA is cleaved from phosphatidylcholine and converted to DG by PA phosphatase. PA and its metabolic derivative, lysophosphatidic acid, are potent mitogens and activators. Therefore, DG kinase and PA phosphatase play crucial roles in regulation of the relative concentration of DG and PA,both of which serve as signal mediators as well as intermediates of glycerolipid synthesis.
The present study disclosed for the first time the heterogeneity of DG kinase in terms of molecular structure, biochemical characteristics and gene expression localization in the brain and clarified the molecular identity of PA phosphatase : Four subtypes of DG kinase (termed type I-IV) were identified by H.Kondo (Head investigator) and h … More is group, its fifth subtype (type delta) was identified by H.Kanoh (co-investigator), its sixth subtype (type thita) by W.J.van Blitterswijk (co-investigator), its seventh by J.A.Glomset (co-investigator), while PA phosphatase (type II) was identified by H.Kanoh. The DG kinase type I is of soluble form and localized in the oligodendrocyte, but not neurons, and the absence of its expression is seen in the brain of myelin-deficient (shiverer) mice, suggesting the role in formation and maintenance of the myelin. The type II DG kinase is of membrane-associated from and localized in the medium-spiny neurons, neurons in the nucleus accumbens and olfactory tubercle, and in the endocrine cells of the pituitary inermediate lobe, suggesting the involvement in the dopaminergic transmission. The type III is localized dominantly in the Purkinje neurons and substantially in the granule cells of the cerebellum, suggesting its role in the cerebellar motor-control. The type IV is localized in the cerebral and cebellar cortical neurons, but peculiar in the molecular structure : while the former three contain two EF-hand and zinc-finger motifs in addition to the ATP-binding domain, the type IV contains no EF-hand motifs, but possesses ankyrin-like repeats. This structure has a high homology to rdgA (a gene of Drosophila inducing the retinal degeneration). A nuclear targeting motif is also contained and the transfection of this cDNA into the fibroblast results in localization of its protein in the nucleus, suggesting its role in the regulation of transcription. The delta type contains a pleckstrin homology domain and a DPH C-terminal tail homology domain, while the thita type contains three cysteine-rich domains, a proline-rich region and a pleckstrin homology domain with overlapping ras-associating domain. The DG kinase subtype by J.A.Glomset is a membrane-bound and selectively phosphrylates arachidonoyl-DG,indicating that this is specific in the PI turnover. The type II PA phosphatase is membrane-bound and its N-terminal sequence is conserved in the partial cDNA of hic53, a H O -inducible gene. Less

Report

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

    (40 results)

All Other

All Publications (40 results)

  • [Publications] 後藤薫と近藤尚武: "104 kDa diacylglycerol kinase containing ankypin-like pepeats localizes in the cell nucleus." Proc.Natl.Acad.Sci.U.S.A.93. 11196-11201 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 後藤薫と近藤尚武: "Heterogeneity of diacylglycerol kinase in terms of molecular structure,biochemical charactenstics and gene expression Socalization in the brain." J.Lipid.Med.14. 251-257 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 中川有,後藤薫と近藤尚武: "Cloning,expression and localization of 230 kDa phosphatidyl inositol 4-kinase." J.Biol.Chem.271. 12088-12094 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 中川有,後藤薫と近藤尚武: "Cloning and characterization of sluble phosphatidylinositol 4-kinase of 92 kDa" Biochem.J.320. 643-649 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 伊東靖,阪上洋行と近藤尚武: "Enhanced gene expression for phosphatidylinositol 3-kinase in the hypoglassal motonewrons following axonal crush." Mol.Brain Res.37. 329-332 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 伊東靖,後藤薫と近藤尚武: "Localization of mRNA for phosphatidyl inositol 3-kinase in brain of developing and mature rats." Mol.Brain Res.34. 149-153 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 阪上洋行,沢村佳宏と近藤尚武: "Spnchronous patohy pattern of gene expression for adenyl cyclase and phosphodiesterase but discrete expression for G-protein in developing rat striatum" Mol.Brain Res.33. 185-191 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] B.Houssa,D.Shaap,J.van der Wal K.Goto,H.Kondo,A.Yamakawa,M.Shibata,T.Takanawa,W.J.van Blitterwijk: "Cloning of a novel human diacylgycerol kinase (DGKO) containing three cystieine-rich domains,a proline-rich region and a Pleekstim homology domain with overlapping Ras-associating domain" J.Biol.Chem.(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fumio Sakane,Shinichi Imai,Masahiro Kai,Tkuo Wada & Hideo Kanoh: "Moleculay cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein tyrosine kinases" J.Biol.Chem.271. 8394-8401 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Kai,I.Wada,S.Imai,F.Sakane & H.Kanoh: "Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type2) bound to plasma membranes" J.Biol.Chem.271. 18931-18938 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Sakane,M.Kai,I.Wada,S.Imai & H.Kanoh: "The C-terminal part of diacylglycerol kinase & lacking zinc fingers serves as a catalytic domain" Biochem.J.318. 583-590 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] I.Wada,M.Kai,S.Imai,F.Sakane & H.Kanoh: "Tpanslocation of diacylglycerol kinase α to the nuclear matirix of pat thymocytes and peripheral T-lymphocytes" FEBS Letters. 393. 48-52 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Yamada,F.Sakane,N.Matsushima & H.Kanoh: "EF-hand motifs of α,β and γ isoforms of diacyl-glycerol kinase bind calcium with different affinities and conformational changes." Biochem.J.321. 59-64 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.K.Higgins & J.A.Glomset: "Pupification and properties of a phosphatidic acid-preferring phospholipase A1 from bovine testis." J.Biol.Chem.271. 10874-10883 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.P.Walsh,R.Suen & J.A.Glomset: "Apadidomoyl-diacylglycerol kinase,Specific in vitro inhibtion by polyphosphoinositides suggests a mechanism for regulation of phosphatidyl inositol biosynthesis." J.Biol.Chem.270. 28647-28653 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Goto & H.Kondo: "104 kDa diacylglycerol kinase containing ankyrin-like repeats localizes in the cell nucleus." Proc.Natl.Acad.Sci.USA.93. 11196-11201 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Goto & H.Kondo: "Heterogeneity of diacylglycerol kinase in terms of molecular structure, biochemical characteristics and gene expression localization in the brain." J.Lipid Med.14. 251-257 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Nakagawa, K.Goto & H.Kondo: "Cloning, expression and localization of 230kDa phosphoinositol 4-kinase" J.Biol.Chem.271. 12088-12094 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Nakagawa, K.Goto & H.Kondo: "Cloning and characterization of soluble phosphatidylinositol 4-kinase of 92 kDa" Biochem.J.320. 643-649 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Ito, H.Sakagami, H.Kondo: "Enhanced gene expression for phosphatidylinositol 3-kinase in the hypoglossal motoneurons following axonal crush." Mol.Brain Res.37. 329-332 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Ito, K.Goto & H.Kondo: "Localization of mRNA for phosphatidylinositol 3-kinase in brain of developing and mature rats." Mol.Brain Res.34. 149-153 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Sakagami, Y.Sawamura, H.Kondo: "Synchronous pathy pattern of gene expression for adenyl cyclase and phosphodiesterase but diserete expression for G-protein in developing rat striatum." Mol.Brain Res.33. 185-191 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] B.Houssa, D.Shaap, J.van der Wal, K.Goto, H.Kondo, A.Yamakawa, M.Shibata, T.Takenawa & W.J.van Blitterswijk: "Cloning of a novel human diacylglycerol kinase (DGkrheta) containing three-cysteine-rich domains, a proline-rich region and a pleckstrin homology domain with overlapping Ras-associating domain" J.Biol.Chem.(In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Sakane, S.Imai, M.Kai, I.Wada & H.Kanoh: "Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH famyly of protein tyrosine kinases" J.Biol.Chem.279. 8394-8401 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Kai, I.Wada, S.Imai, F.Sakane & H.Kanoh: "Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type II) bound to plasma membranes." J.Biol.Chem.271. 18931-18938 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Sakane, M.Kai, I.Wada, S.Imai & H.Kanoh: "The C-terminal part of diacyglycerol kinase alpha lacking zinc fingers serves as a catalytic domain." Biochem.J.318. 583-590 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.P.Walsh, R.Suen & J.A.Glomset: "Arachidonoyl-diacylglycerol kinase, specific in vitro inhibition by phosphoinositides suggests a mechanism for regulation of phosphatidylinositol biosynthesis." J.Biol.Chem.270. 28647-28653 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 加納英雄他4名: "Molecular cloning of a novel diacylglycerol kinase isoame with a pleckstrin homology domain and C terminal tail similar to those of EPH family of protein tyrosine kinase" J. Biol. Chem.271. 8394-8401 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 後藤薫と近藤尚武: "104 kDa diacylglycerol kinase containing ankyrm-like repeats localizes in the cell nucleus." Proc. Natl. Acad. Sci. USA. 93. 11196-11201 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 近藤尚武・後藤薫他1名: "Cloning,expression and localization of 230kDa phosphatidyl inositol 4-kinase" J. Biol. Chem.271. 12088-12094 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 近藤尚武・後藤薫他1名: "Cloning and characterization of soluble phosphatidyl inositol 4-kinase of 92 kDa" Biochem J.320. 643-649 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 近藤尚武・阪上洋行他1名: "Enhanced gene expression for phosphatidylinositol 3-kinase in the hypoglossal motonewons following axonal crush." Mol Brain Res.37. 329-332 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 加納英雄他4名: "Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type 2) bound to plasma membrane" J. Biol. Chem.271. 18931-18938 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 後藤薫・舩山道隆・近藤尚武: "Cloning and expression of a cytoskeleton-associated diacylglycerol kinase that is dominantly expressed in cerebellum." Proc.Natl.Acad.Sci.U.S.A.91. 13042-13046 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] 後藤薫・近藤尚武: "104kDa diacylglycerol kinase containing ankyrin-like repeats localizes in the cell nucleus." Proc.Natl.Acad.Sci.U.S.A.(受領). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 後藤薫・近藤尚武: "Heterogeneity of diacylglycerol kinase in terms of molecular structure, biochemical characteristics and gene expression localization in the brain." J. Lipid Mediator. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] C.C.Farnsworth他3名およびJ.A.Glomset: "Rob geranylgeranyl transferase catalyzes the geranyl-geranylation of adjacent cysteines in the small GTPases Rab 1A,Rab3A and Rab5A." Proc.Natl.Acad.Sci.USA. 91. 11936-11937 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Goto他2名およびH.Kondo,J.A.Glomset20GB05:Cloning and characterization of arachidonyl-specific DG kinase from bovine testis: Proc.Natl.Acad.Sci.USA.(投稿中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Jalink他8名およびW.S.van Blitterswijk: "Lysophatidic acid-induced Ca^<2+> mobilization in human A431 cells:structure-activity analysis" Biochem.J.307. 609-616 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] I.Wada他3名およびH.Kanoh: "Chaperon function of calreticulin when expressed in endoplasmic reticulum as the membrane-anchored and soluble forms." J.Biol Chem.270. 20298-20304 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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