Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3774-3784
Functional Differentiation Signals Mediated by Distinct Regions of the
Cytoplasmic Domain of the Granulocyte Colony-Stimulating Factor
Receptor
Debbie C. Koay and
Alan C. Sartorelli
From the Department of Pharmacology and Developmental Therapeutics
Program, Cancer Center, Yale University School of Medicine, New Haven,
CT.
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 Fc
II/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 FcII/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.
