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 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 FcgammaII/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 FcgammaII/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.
Koay
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DC
Department of Pharmacology and Developmental Therapeutics Program, Cancer Center, Yale University School of Medicine, New Haven, CT, USA.
Sartorelli
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AC
D000818:Animals; D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D051379:Mice; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016177:Macrophage-1 Antigen; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D017452:Receptors, IgG; D016179:Granulocyte Colony-Stimulating Factor