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论文题目: Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells
英文论文题目: Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells
第一作者: Wang, XJ; Qiao, YB; Xiao, MZM; Wang, LB; Chen, J; Lv, WJ; Xu, L; Li, Y; Wang, YM; Tan, MD; Huang, C; Li, JS; Zhao, TC; Hou, ZY; Jing, NH; Chin, YE
英文第一作者: Wang, XJ; Qiao, YB; Xiao, MZM; Wang, LB; Chen, J; Lv, WJ; Xu, L; Li, Y; Wang, YM; Tan, MD; Huang, C; Li, JS; Zhao, TC; Hou, ZY; Jing, NH; Chin, YE
联系作者: Chin, YE (reprint author), Shanghai Jiao Tong Univ, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol,Inst Hlth Sci,Sch Med, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Chin, YE (reprint author), Shanghai Jiao Tong Univ, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol,Inst Hlth Sci,Sch Med, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2017
卷: 18
期: 4
页码: 933-946
摘要: 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.
英文摘要: 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.
刊物名称: CELL REPORTS
英文刊物名称: CELL REPORTS
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 8.282
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论文类别: Article
英文论文类别: Article
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