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Signal transduction mechanisms through granulocyte colony-stimulating factor receptor.

Research Project

Project/Area Number 11680635
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionOkayama University

Principal Investigator

MURAKAMI Hiroshi  Okayama University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (90260174)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordssignal-transduction / gene-expression / receptor / transcription factor / proliferation / differentiation / cell cycle / granulocyte colony-stimulating-factor
Research Abstract

In order to clarify the signal transduction mechanisms of growth suppression during G-CSF induced neutrophil differentiation, gene expressions of cell-cycle regulatory proteins and transcription factors which are involved in granulocyte differentiation were examined in neutrophil progenitor cells GM-162M and 32Dcl3 by Northern blot hybridization. Gene expression of cyclin dependent kinase inhibitor p21^<WAF1> was not increased by G-CSF stimulation, while levels of mRNA for p27^<KIP1> and p19^<INK4D> were elevated. On the other hand, expression of transcription factors C/EBPα and C/EBPε genes, which were possibly involved in the granulocyte differentiation, was induced by G-CSF stimulation, while quantity of PU.1 mRNA was unaffected. Therefore, expression of p27^<KIP1> and p19^<INK4D> appeared to prevent the cell-cycle progression from G1 to S during G-CSF dependent neutrophil differentiation. It's also possible that C/EBPα and/or C/EBPε transcription factors control the gene expression … More of these CDK inhibitors.
We have been trying to identify genes which express in cells capable of responding to G-CSF for neutrophil differentiation but not in the cells with mutant G-CSF receptor unable to respond for the differentiation, thereby being involved in neutrophil differentiation. Using PCR-based subtraction-hybridization technique, several genes were identified including genes for Stat3 and ERO1-L.G-CSF stimulation induces phosphorylation and dimerization of Stat3 which is then transferred to nucleus where Stat3 activates transcription of its target genes. Stat3 activation is known to be necessary for G-CSF dependent neutrophil differentiation. Our data showed that activated Stat3 turns on the expression of its own genes, which produces more Stat3 protein. This mechanism seems to accelerate G-CSF dependent neutrophil differentiation. Moreover, ERO1-L is a enzyme involved in the protein disulfide-bond formation in ER and in formation of tertiary structure of nascent polypeptide. G-CSF dependent expression of ERO1-L gene appeared to be in control of Stat3 activation during neutrophil differentiation. Therefore, ERO1-L seems to help synthesizing bacteriocidal proteins such as MPO and elastase into ER during neutrophil differentiation. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] Inoue,H.: "Targeted disruption of the gene encoding the proteolipid subunit of mouse vacuolar H^+-ATPase leads to early embryonic lethality."Biochimica et Biophysica Acta. 1413. 130-138 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue, H.: "Targeted disruption of the gene encoding the proteolipid subunit of mouse vacuolar H^+-ATPase leads to early embryonic lethality."Biochimica et Biophysica Acta.. 1413. 130-138 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue, H.: "Targeted disruption of the gene encoding the proteolipid subunit of mouse vacuolar H+-ATPase leads to early embryonic lethality"Biochim. Biophys. Act. 1413(3). 130-138 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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