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1992 Fiscal Year Final Research Report Summary

Structure and function of renin and prorenin.

Research Project

Project/Area Number 01060003
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Research InstitutionUniversity of Tsukuba

Principal Investigator

MURAKAMI Kazuo  Univ. of Tsukuba, Inst. of Appl. Biochem., Prof., 応用生物化学系, 教授 (70110517)

Co-Investigator(Kenkyū-buntansha) FUKAMIZU Akiyoshi  Univ. of Tsukuba, Inst. of Appl. Biochem., Instructor, 応用生物化学系, 講師 (60199172)
NAKAYAMA Kazuhisa  Univ. of Tsukuba, Inst. of Biol.Sci., Instructor, 生物科学系, 講師 (40192679)
Project Period (FY) 1989 – 1992
KeywordsRenin / Prorenin / Angiotensinogen / X ray analysis / Embryonic Engineering / Processing / Transgenic mice / Hypertension
Research Abstract

1) X ray structure of renin
Three-dimensional structure of mouse submaxillary renin and recombinant human renin have been determined at 2.5A^^゚ - 3.0A^^゚ resolution by X-ray analysis.
2) Processing enzymes
The cDNA of prorenin processing enzyme in mouse submaxillary glands was cloned and its complete nucleotide sequence was determined, identify that prorenin processing enzyme is identical with proEGF processing enzyme. The processing enzyme processed the submaxillary prorenin to renin, but not kidney prorenin suggesting its organ specificity.
Several candidates (yeast Kex2 like processing enzyme) for kidney prorenin processing enzyme or for prohormones and proenzymes have been identified and their complete amino acid sequences have been determined. These results suggests that not only prorenin but also prohormones and proenzymes are processed by substrate- or organ-specific manner.
3) Gene regulation of renin and angiotensinogen in vivo
Human renin and human angiotensinogen genes both separately and in concert have been introduced into mice by cross-mating.
Strains carring both the human genes demonstrated a chronically sustained increase in blood pressure. Thus, we have established new transgenic mice (Tsukuba Hypertensive Mice) as the first model of human high renin hypertension.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Won-Sin KIM: "A processing enzyme for prorenin in mouse submandibular gland." J.Biol. Chem.265. 5930-5933 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akiyoshi FUKAMIZU: "Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter." J.Biol. Chem.265. 7576-7582 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhisa NAKAYAMA: "Substrate specificity of prorenin converting enzyme of mouse submandibular gland:analysis using site-directed mutagenesis." J.Biol. Chem.265. 21027-21031 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Won-Sin KIM: "Mouse submandibular gland prorenin-converting enzyme is a member of grandular kallikrein family." J.Biol. Chem.266. 19283-19287 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. BADASSO: "Crystallization and preliminary X-ray analysis of complexes of peptide inhibitors with human recombinant and mouse submandibular renins." J.Biol. Chem.223. 447-453 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Detlev GANTEN: "Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes." Proc. Natl. Acad. Sci. USA. 89. 7806-7810 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuo MURAKAMI: "Molecular structure and characterization of renins and their genes in ″The Frontiers of Nephrology″" Elsevier Sci. Publ., 101-110 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akiyoshi FUKAMIZU: "Use of transgenic animals in the study of neurooeotide genes. Recombinant DNA Technologies in Neuroendocrinology Current Topics in Neuroendocrinology." Springer-Verlag Berlin Heidelberg, 146-167 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Won-Sin KIM: "A processing enzyme for prorenin in mouse submandibular gland." J Biol. Chem.265. 5930-5933 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akiyoshi FUKAMIZU: "Structure and expressing of the human angiotensinogen gene. Identification of a unique and highly active promoter." J. Biol. Chem.265. 7576-7582 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuhisa NAKAYAMA: "Substrate specificity of prorenin converting enzyme of mouse submandibular gland : analysis using site-directed mutagenesis." J. Biol. Chem.265. 21027-210131 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Won-Sin KIM: "Mouse submandibular gland prorenin-converting enzyme is a member of grandular kallikrein family." J. Biol. Chem.266. 19283-19287 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. BADASSO: "Crystallization and preliminary X-ray analysis of complexes of peptide inhibitors with human recombinant and mouse submandibular renins." J. Mol. Biol.223. 447-453 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Detlev GANTEN: "Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes." Proc. Natl. Acad. Sci. USA. 89. 7806-7810 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuo MURAKAMI: "Molecular structure and characterization of renins and their genes in "The Frontiers of Nephrology"" Elsevier Sci. Publ.101-110 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akiyoshi FUKAMIZU: "Use of transgenic animals in the study of neuropeptide genes. Recombinant DNA Technologies in Neuroendocrinology. Current Topics in Neuroendocrinology." Springer-Verlag Berlin Heidelberg. 11. 146-167 (1993)

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

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Published: 1994-03-24  

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