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

1997 Fiscal Year Final Research Report Summary

Role of ADP ribosylation factor (ARF) in platelet fanctions

Research Project

Project/Area Number 08671246
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionSAPPORO MEDICAL UNIVERSITY

Principal Investigator

TERUI Takeshi  SAPPORO MEDICAL UNIVERSITY, 医学部, 助手 (50281233)

Co-Investigator(Kenkyū-buntansha) SAKAMAKI Sumio  SAPPORO MEDICAL UNIVERSITY,assistant professor, 医学部, 講師 (00196081)
Project Period (FY) 1996 – 1997
KeywordsADP ribosylation factor / phospholipase D / pletelet / brefeldine A (BFA) / beta-thromboglobulin / aggregation / ADP / collagen
Research Abstract

Stimulation of phospholipase D (PLD) after activation of cell surface receptors has been reported in many cell types. We have investigated the mechanisms of activation of this enzyme, especially ADP ribosylation factor (ARF) dependent PLD,by ADP or collagen in human pletelet. aggregation is still unclearinduced with agonists has been studied.
We examined the expression of ADP ribosylation factor (ARF) in pletelets by immuboblotting and ARF dependent type PLD (PLD1) by RP-PCR.Then, we revealed that both ADP and collagen indused ARF1 activation ([^<35>S]GTPgS binding) on pletelets membrane upto 10-fold. PLD activity on platelet membrane was stimulated 4- to 5- fold by the addition of GTPgammaS and myrisoylated recombinant ARF1. And both ADP and collagen also induced ARF dependent PLD activity about 150%.
Brefeldine A (BFA) inhibits activation of ARF and PLD about 40% and 50% respectively, aggregation of platelets by ADP,however, was not inibited so much (only 25% inhibition). However, BFA inhibited 50% of maxmal aggreation of platelets by collagen. Considering ADP induces primary aggregation and collagen induces secondary aggregation of platelete, BFA might have inhibited granule relese and so on. BFA inhibited 60% of beta-TG release from platelet.
In conclution, ARF-PLD signaling seems to be under GPIa/IIa or GPIb/V/IX as collagen receptor and work as a signal transduction for granule release and platelet aggregation.

  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Randazzo P.A.et al: "The myristoylaed amino terminus of ADP-ribosylation factor 1 is a phospholipid and GTP-senstive switch." J.Biol.Chem.270. 14809-14815 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terui T.et al: "Effect of Acid phospholipids on nucleotide exchange properties of ADP-ribosylation factor 1" J.Biol.Chem.269. 28130-28135 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kahn R.A.et al: "Mutationl analysis of Saccharomyces cerevisiae ARF1." J.Biol.Chem.270. 143-150 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Cavenagh M.M.et al: "ADP-ribosylation factor(ARF)-like 3,a new member of the ARF family of GTP-binding proteins cloned from human and rat tissues." J.Biol.Chem.269. 18937-18942 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakamaki S.et al: "Long term survaival and differentiation of human poripheral blood CD34+ cells in SCID mice." Int J Hematol.69. 375-384 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Randazzo R.A.et al: "The amino terminus of ADP-ribosylation factor(ARF)1 is essential for interaction with Gs and ARF GTPase-activating protein." J.Biol.Chem.269. 29490-29494 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakamaki S., Hayashi S., Takayanagi N., Niitsu Y.: "Auto antibodies in sera of patients with UC recongnize tropomyosin peptide associated with HLA-DPw9" Gastroenterol. 110. A1007 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terui T., Muraskami T., Takimoto R.Hirayama A., Kato J., Niitsu Y.: "ADP ribosylation factor-phospholipase D signaring and its immplication in cell growth of human cancer cells." Jap.J.Cancer.Res.88 ; sup.299 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato J., Takimoto R., Terui T., Nittsu Y.: "Dysfunction of p53 is one of mechanism for growth escape of human stomach cancer from negative regulation by TGF-beta. In ; Tahara, E., Sugimachi, K., Oohara, T., editors." Recent Advances in Gastroenterological Carcinogenesis I.Bologna, Mnduzzi, Editore.107-112 (1996)

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

URL: 

Published: 1999-03-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi