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Signal transduction mechanisms of neutrophil differentiation through G-CSF receptor.

Research Project

Project/Area Number 14580700
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

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

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordssignal transduction / colony stimulating factor / receptor / proliferation / differentiation / neutrophil / cytokine / granulocyte
Research Abstract

G-CSF stimulation leads to the myeloid precursor cells to proliferate for a few days, then they stop proliferating, followed by differentiation to the mature neutrophils. The tyrosine residues in membrane-distal region of the G-CSF receptor as well as the activation of STAT3 was involved in the growth arrest during the neutrophil differentiation. However, involvement of other residues of the receptor and other signaling molecules in the growth arrest remains to be determine. We introduced mutations in the cytoplasmic region of the receptor and transfected them into granulocyte precursor cells which did not express endogenous G-CSF receptor. A cell line was isolated that proliferated continuously in the presence of G-CSF, that is, that did not show growth-arrest in the medium containing G-CSF. The mutated G-CSF receptor genes were isolated by PCR from the chromosomal DNA of the obtained cell line. Each mutant gene was re-introduced into the granulocyte precursor cells and G-CSF-response … More s of the obtained stable transformants were examined. A cell line which proliferated continuously in the medium with G-CSF, carved G-CSF receptor with its 59 amino acid deletion in its C-terminus, suggesting this C-terminus domain is responsible for transducing the growth arrest signals. A series of truncated receptors were constructed and cell lines expressing these truncated receptors were established. G-CSF-responses of the cell lines harboring these truncated receptors revealed that C-terminal 25 amino acid residues of the G-CSF receptor was necessary for the transducing growth arrest signals. Cells expressing the truncated receptors also showed the defects in the G-CSF-dependent induction of neutrophilic morphological changes with lobulated nucleus. The G-CSF dependent activation of STATS was prolonged in the cells expressing the truncated receptor. Therefore, the C-terminal 25 amino acid residues were responsible for the sustained activation of STAT5, resulting in the defects in the G-CSF dependent growth arrest and morphological changes. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] 村上 宏: "生物工学会誌 第82巻 第4号"日本生物工学会(印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiroshi Murakami: "Neurotrophil differentiation with morphological changes by G-CSF stimulation."Seibutsu-Kogaku Kaishi (Japanese). Vol.4(in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Omura, T., et al.: "Acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation by overexpression of Lyn tyrosine kinase"European J. Biochem. 269. 381-389 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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