LIF promotes self-renewal of mouse embryonic stem cells (mESCs), and in its absence, the cells differentiate. LIF binds to the LIF receptor (LIFR) and activates the JAK-STAT3 pathway, but it remains unknown how the receptor complex triggers differentiation or self-renewal. Here, we report that the LIFR cytoplasmic domain contains a self-renewal domain within the juxtamembrane region and a differentiation domain within the C-terminal region. The differentiation domain contains four SPXX repeats that are phosphorylated by MAPK to restrict STAT3 activation; the self-renewal domain is characterized by a 3K motif that is acetylated by p300. In mESCs, acetyl-LIFR undergoes homodimerization, leading to STAT3 hypo- or hyper-activation depending on the presence or absence of gp130. LIFR-activated STAT3 restricts differentiation via cytokine induction. Thus, LIFR acetylation and serine phosphorylation differentially promote stem cell self-renewal and differentiation.
基金：
National Natural Science Foundation of
China (grants 81230059 and 31271367); 973 grants (2013CB910900
and 2013CB510105), and Chinese Academy of Science starting grant
(2011CSP002). X.J.W. also received a postdoctoral fellowship from Jiaotong
University School of Medicine and was supported by the National Natural Science
Foundation of China (grants 31671415 and 81372028).
Wang Xiong-jun,Qiao Yunbo,Xiao Minzhe M.,et al.Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells[J].CELL REPORTS.2017,18(4):933-946.doi:10.1016/j.celrep.2016.12.081.
APA：
Wang, Xiong-jun,Qiao, Yunbo,Xiao, Minzhe M.,Wang, Lingbo,Chen, Jun...&Chin, Y. Eugene.(2017).Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells.CELL REPORTS,18,(4)
MLA：
Wang, Xiong-jun,et al."Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells".CELL REPORTS 18..4(2017):933-946
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