TY - JOUR
T1 - The cytoplasmic domain of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor α subunit is essential for both GM-CSF-mediated growth and differentiation
AU - Matsuguchi, Tetsuya
AU - Zhao, Yanming
AU - Lilly, Michael B.
AU - Kraft, Andrew S.
PY - 1997
Y1 - 1997
N2 - Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates differentiation, survival, and proliferation of colony-forming unit- granulocyte-macrophage progenitor cells. The biologic actions of GM-CSF are mediated by binding to a specific receptor consisting of two chains designated as α and β subunits. We have demonstrated that the murine FDC- P1-derived cell line WT-19 transfected with the human GM-CSF receptor and β subunits (GM-CSFRα and β) can be induced to differentiate by the addition of human GM-CSF (hGM-CSF). By expressing a series of GM-CSFRα mutants in WT19 cells, we have determined the amino acid domains of the GM-CSFRα cytoplasmic domain that regulate cell differentiation, proliferation, and survival. We found that the membrane proximal proline-rich domain and adjacent 16 residues are essential for both hGM-CSF-dependent cell proliferation and differentiation. In contrast, the C-terminal region of the GM-CSFRα cytoplasmic domain was not necessary for cell differentiation mediated by hGM-CSF, but the removal of this region severely impaired the ability of hGM-CSF to support cell survival. While the activation of JAK2, Shc, Erk, and STAT5 proteins correlated with hGM-CSF-mediated cell growth, cellular differentiation occurred in the absence of activation of these signal transduction pathways.
AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates differentiation, survival, and proliferation of colony-forming unit- granulocyte-macrophage progenitor cells. The biologic actions of GM-CSF are mediated by binding to a specific receptor consisting of two chains designated as α and β subunits. We have demonstrated that the murine FDC- P1-derived cell line WT-19 transfected with the human GM-CSF receptor and β subunits (GM-CSFRα and β) can be induced to differentiate by the addition of human GM-CSF (hGM-CSF). By expressing a series of GM-CSFRα mutants in WT19 cells, we have determined the amino acid domains of the GM-CSFRα cytoplasmic domain that regulate cell differentiation, proliferation, and survival. We found that the membrane proximal proline-rich domain and adjacent 16 residues are essential for both hGM-CSF-dependent cell proliferation and differentiation. In contrast, the C-terminal region of the GM-CSFRα cytoplasmic domain was not necessary for cell differentiation mediated by hGM-CSF, but the removal of this region severely impaired the ability of hGM-CSF to support cell survival. While the activation of JAK2, Shc, Erk, and STAT5 proteins correlated with hGM-CSF-mediated cell growth, cellular differentiation occurred in the absence of activation of these signal transduction pathways.
UR - http://www.scopus.com/inward/record.url?scp=0030794017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030794017&partnerID=8YFLogxK
U2 - 10.1074/jbc.272.28.17450
DO - 10.1074/jbc.272.28.17450
M3 - Article
C2 - 9211889
AN - SCOPUS:0030794017
SN - 0021-9258
VL - 272
SP - 17450
EP - 17459
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 28
ER -