Journal
CELL REPORTS
Volume 18, Issue 4, Pages 933-946Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.12.081
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Funding
- National Natural Science Foundation of China [81230059, 31271367, 31671415, 81372028]
- 973 grants [2013CB910900, 2013CB510105]
- Chinese Academy of Science starting grant [2011CSP002]
- Jiaotong University School of Medicine
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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.
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