Functional Differentiation Signals Mediated by Distinct Regions of the Cytoplasmic Domain of the Granulocyte Colony-Stimulating Factor Receptor

Granulocyte colony-stimulating factor receptor (G-CSFR) regulates the proliferation and differentiation of neutrophilic progenitor cells through interaction with its cytokine. Exposure of WEHI-3B D+ myelomonocytic leukemia and myeloid LGM-1 cells overexpressing the G-CSFR to G-CSF resulted in induct...

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Veröffentlicht in:Blood 1999-06, Vol.93 (11), p.3774-3784
Hauptverfasser: Koay, Debbie C., Sartorelli, Alan C.
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description Granulocyte colony-stimulating factor receptor (G-CSFR) regulates the proliferation and differentiation of neutrophilic progenitor cells through interaction with its cytokine. Exposure of WEHI-3B D+ myelomonocytic leukemia and myeloid LGM-1 cells overexpressing the G-CSFR to G-CSF resulted in induction of differentiation as measured by (1) the ability to reduce nitroblue tetrazolium (NBT), (2) the expression of Mac-I antigen, and (3) the expression of FcγII/III receptor. Mutational analyses indicated that distinct regions of the cytoplasmic domain were critical for efficient induction of each functional marker. The membrane proximal region containing homology sequences of boxes 1 and 2 was important for the activation of all three functional markers of mature neutrophils. Induction of the capacities to express Mac-I antigen or FcγII/III receptor also required additional sequences in the membrane proximal region between amino acids 70 and 100 and may be dependent on the phosphorylation of Tyr703. The findings suggest that distinct sequences within the amino-terminal region of the cytoplasmic domain of the receptor are sufficient to induce these functional markers of differentiation, and receptor tyrosine phosphorylation may be necessary.
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source MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Animals
Biological and medical sciences
Cell Differentiation
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
DNA Mutational Analysis
Fundamental and applied biological sciences. Psychology
Granulocyte Colony-Stimulating Factor - metabolism
Granulocyte Colony-Stimulating Factor - pharmacology
Macrophage-1 Antigen - biosynthesis
Mice
Molecular and cellular biology
Receptors, Granulocyte Colony-Stimulating Factor - genetics
Receptors, Granulocyte Colony-Stimulating Factor - metabolism
Receptors, IgG - biosynthesis
Signal Transduction - drug effects
Tumor Cells, Cultured
title Functional Differentiation Signals Mediated by Distinct Regions of the Cytoplasmic Domain of the Granulocyte Colony-Stimulating Factor Receptor
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