The cytoplasmic domain of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit is essential for both GM-CSF-mediated growth and differentiation

被引:60
作者
Matsuguchi, T
Zhao, YM
Lilly, MB
Kraft, AS
机构
[1] UNIV COLORADO,HLTH SCI CTR,DIV MED ONCOL,DENVER,CO 80262
[2] UNIV KENTUCKY,DEPT BIOCHEM,LEXINGTON,KY 40536
[3] UNIV WASHINGTON,DIV MED ONCOL,SEATTLE,WA 98108
[4] VET ADM MED CTR,SEATTLE,WA 98108
关键词
D O I
10.1074/jbc.272.28.17450
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha and beta subunits. We have demonstrated that the murine FDC-P1-derived cell line WT-19 transfected with the human GM-CSF receptor alpha and beta subunits (GM-CSFR alpha and beta) can be induced to differentiate by the addition of human GM-CSF (hGM-CSF). By expressing a series of GM-CSFR alpha 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-CSFR alpha 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.
引用
收藏
页码:17450 / 17459
页数:10
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