• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pathobiological Study on Congenital Deficiency of Vitamin K-dependent Protein S.

Research Project

Project/Area Number 62480433
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Laboratory medicine
Research InstitutionThe University of Tokushima (1989)
Mie University (1987-1988)

Principal Investigator

SUZUKI Koji  Institute for Enzyme Research, University of Tokushima, 酵素科学研究センター, 教授 (70077808)

Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsProtein S / Protein C / C4b-binding protein / Congenital protein S deficiency / Congenital thrombophilia / Protein C anticoagulant pathway / Vitamin K-dependent proteins / Monoclonal antibody / C_4b結合蛋白質(C_4bp) / PS・C_4bp複合体 / 遊離型プロテインS / 先天性プロテインS欠損症 / C_<4b>結合蛋白質(C_<4bp>) / 血液凝固制御因子
Research Abstract

[Aim] Protein S is a vitamin K-dependent plasma protein that plays a role as a cofactor for activated protein C (APC). APC is another vitamin K-dependent serine protease which inactivates blood coagulation cofactors, Factor Va and Factor VIIIa. Recently, patients with congenital deficiency of protein S or protein C have frequently been found as patients having severe thromboembolic diseases. Thus, protein S is involved in concert with APC in regulation of blood coagulation in vivo as well as in vitro. Recently, protein S in plasma was found to exist in two forms, one is a functionally active free form and the other is a functionally inactive complex form with a complement.component C4b-binding protein (C4bp) . The present study was performed to elucidate the pathobiology of protein S in patients with congenital deficiency of protein S.
[Results and Discussion] (1) Thirty seven patients in two families with congenital protein S deficiency were analyzed, then it was found that plasma protein S activity in these patients appeared to correlate with the amount of-free form protein S, but not with that of total protein S nor C4bp. (2) Seventeen monoclonal antibodies for C4bp were prepared and their epitopes on C4bp molecule were determined. Also a binding site for protein S on C4bp was determined. (3) Fifteen monoclonal antibodies for protein S were prepared and epitopes for the respective antibodies were determined. Enzyme immunoassay methods to determine free form protein S, total protein S and protein S-C4bp complex were established. (4) Function of protein S-C4bp complex was investigated and it was found that the complex inhibits competitively the interaction between free form protein S and APC which results in the decrease of cofactor activity of free form protein S. These results indicate that in plasma of patients with congenital deficiency of protein S, the cofactor activity of protein S depends on the amounts of both free form and complex form of protein S.

Report

(4 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Ogura,M.,Tanabe,N.,Nishioka,J.& Suzuki,K.: "Biosynthesis and secretion of functional protein S by a human megakaryoblastic cell line(MEG-01)" Blood. 70. 301-306 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suzuki,K.& Nishioka,J.: "Plasma protein S activity measured using Protac,a snake venom derived activator of protein C." Thromb.Res.49. 241-251 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 鈴木宏治,神谷忠: "先天性プロテインS欠損症" 日本血液学会雑誌. 51. 1298-1301 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suzuki,K.& Nishioka,J.: "Binding site for vitamin K-dependent protein S on complement,C_4b-binding protein." J.Biol.Chem.263. 17034-17039 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Iijima,K.,Inoue,N.,Nakamura,K.et al.: "Inherited deficiency of functional and free from protein S." Acta Haematol.Jpn.52. 126-136 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Nishioka,J.& Suzuki,K.: "Inhibition of cofuctor activity of protein S by a complex of protein S and C_4b-binding protein:Evidence for an inactive ternary complex formation between protein S,C_4b-binding protein and activated protein C." J.Biol.Chem.(in press). 265. (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ogura, M., Tanabe, N., Nishioka, J., Suzuki, K. & Saito, H.: "Biosynthesis and secretion of functional protein S by a human megakaryoblastic cell line (MEG-01)." Blood 7: 301-306, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suzuki, K. & Nishioka, J.: "Pathobiological and clinical significance of immunological determination of plasma protein S." Jpn. J. Clin. Pathol. 35: 1402-1407, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suzuki, K. & Nishioka, J.: "Plasma protein S activity measured using Protac, a snake venom derived activator of protein C." Thromb. Res. 49: 241-251, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suzuki, K. & Kamiya, T.: "Congenital deficiency of protein S." Acta Haematol. Jpn. 51: 1298-1301, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suzuki, K. & Nishioka, J.: "Interaction site of activated protein C and protein S. In: Current Advances in Vitamin K Research (Suttie, J.W. ed.)." Elsevior Science Publishing Co., Inc. Amsterdam. pp.129-133.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Suzuki, K. & Nishioka, J.: "Binding site for vitamin K-dependent protein S on complement C4b-binding protein." J. Biol. Chem. 263: 17034-17039, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Iijima, K., Inoue, N., Nakamura, K., Fukuda, C., Ohgi, C., Okada, M., Mori, T., Nishioka, J., Hayashi, T. & Suzuki, K.: "Inherited deficiency of functional and free form protein S." Acta Haematol. Jpn. 52: 126-133, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Nishioka, J. & Suzuki, K.: "Inhibition of cofactor activity of protein S by a complex of protein S and C4b-binding protein: Evidence for an inactive ternary complex formation between protein S, C4b-binding protein and activated protein C." J. Biol. Chem. 265: 1990.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ogura,M.,Tanabe,N.,Nishioka,J.& Suzuki,K.: "Biosynthesis and secretion of functional protein S by a human megakaryoblastic cell line(MEG-01)." Blood. 70. 301-306 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suzuki,K.& Nishioka,J.: "Plasma protein S activity measured using Protac,a snake venom derived activator of protein C." Thromb.Res.49. 241-251 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] 鈴木宏治,神谷忠: "先天性プロテインS欠損症" 日本血液学会雑誌. 51. 1298-1301 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suzuki,K.& Nishioka,J.: "Binding site for vitamin K-dependent protein S on complement C_4b-binding protein." J.Biol.Chem.263. 17034-17039 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Iijima,K.,Inoue,N.,Nakamura,K.et al.: "Inherited deficiency of functional and free from protein S." Acta Haematol.Jpn.52. 126-136 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Nishioka,J.& Suzuki,K.: "Inhibition of cofactor activity of protein S by a complex of protein S and C_4b-binding protein:Evidence for an inactive ternary complex formation between protein S,C_4b-binding protein and activated protein C." J.Biol.Chem.265. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suzuki,K.: Thrombosis Research. 49. 241-252 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Suzuki,K.: Journal of Biochemistry. 104. 628-632 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Suzuki,K.: Journal of Biological Chemistry. 263. 17034-17039 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 鈴木宏治: 蛋白質・核酸・酵素. 33. 1003-109 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 鈴木宏治: 日本血液学会雑誌. 51. 1298-1301 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 西岡淳二: 検査と技術. 7. 858-869 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Ogura,T.;Tanabe,N.;Nishioka,J.;Suzuki,K.;Saito,H.: Blood. 70. 301-306 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Suzuki,K.;Deyashiki,Y.;Nishioka,J.;Akira,M.;Kurachi,K.;Hashimoto,S.: J.Biol.Chem.262. 611-616 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 鈴木宏治: Theraputic Research. 7. 1318-1325 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 鈴木宏治: 臨床科学. 23. 729-736 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 鈴木宏治;神谷忠: 臨床病理. 35. 514-518 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 鈴木宏治: 日本臨床・特集分子血液学. 45. 2971-2982 (1987)

    • Related Report
      1987 Annual Research Report

URL: 

Published: 1987-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi