1996 Fiscal Year Final Research Report Summary
G-CSF-induced proliferation and differentiation of neutrophils
| Project/Area Number |
07457014
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Osaka University |
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Principal Investigator |
NAGATA Shigekazu Osaka University Medical School, Professor, 医学部, 教授 (70114428)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Hiroshi Okayama University Faculty of Engineering, Associate Professor, 工学部, 助教授 (90260174)
FUKUNAGA Rikiro Osaka University Medical School, Associate Professor, 医学部, 助教授 (40189965)
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| Project Period (FY) |
1995 – 1996
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| Keywords | neutrophils / granulocyte-colony stimulating factor / signal tranduction / cytokine and its receptor / celluar proliferation and differentiation / transcription factors / tyrosine phosphorylation / gene expression |
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| Research Abstract |
Neutrophils in blood are generated from stem cells through various intermediate cells. Proliferation and differentiation of the progenitor cells of neutrophils are specifically regulated by granulocyte colony-stimulating factor (G-CSF). Previously, we have isolated cDNA for G-CSF and G-CSF receptor, and elucidated their structure. By introducing the cloned G-CSF receptor cDNA in mouse myeloid precursor cells which normally do not express the G-CSF receptor, we identified two distinct functional domains in the G-CSF receptor for proliferation and differentiation. The differentiation signal included the specific gene induction of myeloperoxidase or leukocyte elastase which are normally expressed in neutrophils. The cytoplasmic region of the G-CSF receptor contains 4 tyrosine residues, which are phosphorylated upon binding of G-CSF.Mutational analysis of these tyrosine residues indicated that each tyrosine residue has a distinct role to transduce the signals which lead to the neutrophil differentation. We showed that Jak1 and Jak2 kinases as well as STAT3 transcription factor are specifically activated upon binding of G-CSF to the receptor. Using the dominant-negative form of STAT3, we could show that STAT3 is involved in the G-CSF-induced differentiation signal, in particular, in the G-CSF-induced morphological changes of the neutrophilic granulocytes. Development and differentiation of cell are often determined by transcription factors containing zinc-finger domains. We have isolated a novel form of myeloid zinc-finger protein (MZF).
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