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Cellular Signal Transduction by Isoprenoids

Research Project

Project/Area Number 08680649
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionNiigata University

Principal Investigator

FUJII Hiroshi  Niigata University School of Medicine Associate Professor, 医学部, 助教授 (90165340)

Co-Investigator(Kenkyū-buntansha) ONO Teruo  Niigata University School of Medicine Professor, 医学部, 教授 (00000927)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsposttranslational lipid modification / protein modification / ras / isoprenoid / signal transduction / molecular chaperon / Ras
Research Abstract

One of the unanswered questions in this project is the presumed role that prenylation plays in targeting many proteins to specific cellular membranes. While ras and most heterotrimeric G proteins are specifically localized to the plasma membrane, other prenylated proteins, such as members of the rab family, are predominantly localized on intracellular membranes. Scince these differences in localization cannot be accounted for by distinct isoprenoids (farnesylation or geranylgeranylation), additional determinants must be involved. One possibility is that specific receptors on membranes would recognize both the isoprenoid and an additional region of a particular protein. Another possibility is that a prenylated protein could be recognized by a putative molecular chaperon which would direct it to a specific membrane. Elucidating the molecular mechanisms should provide new insight into the importance of prenylation in intracellular signal transduction by isoprenylated proteins. We report the identification, purification, and characterization of proteins that interact with farnesyl moiety of ras protein. The proteins were purified from rat brain cytosol through use of an affinity column containing the farnesylated heptapeptide (SKTKC) corresponding to the COOH-terminal 5 amino acids of Ki-ras. Major two proteins were purified by this chromatography. One has an apparent molecular weight of 50,000, termed P50, and that of another protein (P90) is 90,000 on SDS-polyacrylamide gel electrophoresis. Sequence analysis of lysyl endopeptidase-released peptides from these proteins revealed that P50 is a mixture of alpha, beta-tubulin and P90 is a mixture of alpha, beta-heat shock proteins 90 (hsp90). Further study is required to elucidate physiological function of these proteins interacting with the farnesyl moiety of ras protein.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Kanda, T: "Intestinal fatty acid-binding protein is a useful diagnostic marker for mesentric infarction in human" Gastroenterology. 110. 339-343 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kanda, T: "Eqffect of bile on the intestinal bile acid-binding protein (I-BABP) expression. In vitro and in vivo studies" FEBS Lett.384. 131-134 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe, R.: "Expression of cutaneous fatty acid-binding protein and its mRNA in rat skin" Arch.Dermatol.Res.288. 481-483 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujii, H.: "Fatty Acid-binding Protein,FABP" J.Jpn.Atheroscler.24. 353-361 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujii, H.: "Phospholipid Transfer Protein,PL-TP" J.Jpn.Atheroscler.24. 781-789 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe, R.: "Immunohistochemical distribution of cutaneous fatty acid-binding protein in human skin" J.Dermatol.Sci.16. 17-22 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kanda, T.: "Regulation of the expression of human intestinal bile acid-binding protein in Caco-2 cells" Biochem.J.330. 261-265 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe, R.: "Expression and characterization of rat cutaneous fatty acid-binding protein" J.Biol.Chem.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi, H.: "High transepidermal water loss induces fatty acid synthesis and cutaneous fatty acid-binding protein expression in rat skin" J.Dermatol.Sci.( in press ). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kanda, T.: "Intestinal fatty acid-binding protein is a useful diagnostic marker for mesentric infarction in human." Gastroenterology. 110. 339-343 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kanda, T.: "Effect of bile on the intestinal bile acid-binding protein (I-BABP) expression. In vitro and in vivo studies." FEBS Lett.384. 131-134 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe, R.: "Expression of cutaneous fatty acid-binding protein and its mRNA in rat skin." Arch.Dermatol.Res.288. 481-483 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujii, H.: "Fatty Acid-binding Protein, FABP." J.Jpn.Atheroscler. 24. 353-361 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujii, H.: "Phospholipid Transfer Protein, PL-TP." J.Jpn.Atheroscler. 24. 781-789 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe, R.: "Immunohistochemical distribution of cutaneous fatty acid-binding protein in human skin." J.Dermatol.Sci.16. 17-22 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kanda, T.: "Regulation of the expression of human intestinal bile acid-binding protein in Caco-2 cells." Biochem.J.330. 261-265 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe, R.: "Expression and characterization of rat cutaneous fatty acid-binding protein." J.Biol.Chem.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi, H.: "High transepidermal water loss induces fatty acid synthesis and cutaneous fatty acid-binding protein expression in rat skin." J.Dermatol.Sci. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kanda,T.: "Intestinal fatty acid-binding protein is a useful diagnostic marker for mesentric infarction in human" Gastroenterology. 110. 339-343 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kanda,T.: "Effect of bile on the intestinal bile acid-binding protein(I-BABP)expression.In vitro and in vivo studies" FEBS Lett.384. 131-134 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe,R.: "Expression of cutaneous fatty acid-binding protein and its mRNA in rat skin" Arch.Dermatol.Res.288. 481-483 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii,H.: "Fatty Acid-binding Protein,FABP" J.Jpn.Atheroscler.24. 353-361 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii,H.: "Phospholipid Transfer Protein,PL-TP" J.Jpn.Atheroscler.24. 781-789 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe,R.: "Immunohistochemical distribution of cutaneousfatty acid-binding protein in human skin" J.Dermatol.Sci.16. 17-22 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kanda,T.: "Regulation of the expression of human intestinal bile acid-binding protein in Caco-2 cells" Biochem.J.330. 261-265 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe,R.: "Expression and characterization of rat cutaneous fatty acid-binding protein" J.Biol.Chem.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamaguchi,H.: "High transepidermal water loss induces fatty acid synthesis and cutaneous fatty acid-binding protein expression in rat skin" J.Dermatol.Sci.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kanda,T.: "Intestinal fatty acid-binding protein is a useful diagnostic marker for mesentric infarction in human." Gastroenterology. 110. 339-343 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kanda,T.: "Effect of bile on the intestinal bile acid-binding protein (I-BABP) expression. In vitro and in vivo studies." FEBS Lett.384. 131-134 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sato,E.: "Tissue-specific regulation of the expression of rat intestinal bile acid-binding protein." FEBS Lett.374. 184-186 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujita,M.: "Molecular cloning,expression and characterization of a human intestinal 15 kDa protein." Eur. J. Biochem.233. 406-413 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iseki,S.: "Immunochemical localization of two types of fatty acid-binding proteins in rat overies during postnatal development and immature rat overies treated with gonadotropins." Anat. Rec.241. 235-243 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakai,K.: "Tissue-specific suppression of aortic fatty acid-binding protein in streptozotocin induced diabetic rats." Eur. J. Biochem.229. 201-206 (1995)

    • Related Report
      1996 Annual Research Report

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

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