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J Biol Chem. 1998 Jul 31;273(31):19411-8.

Cytoplasmic domains of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor beta chain (hbetac) responsible for human GM-CSF-induced myeloid cell differentiation.

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1
Division of Medical Oncology, University of Colorado Health Science Center, Denver, Colorado 80262, USA.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates differentiation, survival, and proliferation of myeloid progenitor cells. The biologic actions of GM-CSF are mediated by its binding to the alpha and beta subunits of the GM-CSF receptor (GM-CSFRalpha and betac, respectively). To determine whether identical regions of the betac protein mediate both cell growth and differentiation, we expressed cDNA constructs encoding the human wild-type (897 amino acids) and truncated betac (hbetac) subunits along with the wild-type human GM-CSFRalpha subunit in the murine WT19 cell line, an FDC-P1-derived cell line that differentiates toward the monocytic lineage in response to murine GM-CSF. Whereas the WT19 cell line carrying the C-terminal deleted hbetac subunit of 627 amino acids was still able to grow in human GM-CSF (hGM-CSF), 681 amino acids of the hbetac were necessary for cell differentiation. The addition of hGM-CSF to WT19 cell lines containing the hbetac627 subunit stimulated the phosphorylation of ERK (extracellular signal-regulated kinase) and induced the tyrosine-phosphorylation of SHP-2 and STAT5, suggesting that the activation of these molecules is insufficient to mediate the induction of differentiation. A point mutation of tyrosine 628 to phenylalanine (Y628F) within hbetac681 abolished the ability of hGM-CSF to induce differentiation. Our results indicate that the signals required for hGM-CSF-induced differentiation and cell growth are mediated by different regions of the hbetac subunit.

PMID:
9677359
DOI:
10.1074/jbc.273.31.19411
[Indexed for MEDLINE]
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