Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells | Zendy

Xiong-jun Wang | Zendy; Yunbo Qiao | Zendy; Minzhe M. Xiao | Zendy; Lingbo Wang | Zendy; Jun Chen | Zendy; Wenjian Lv | Zendy; Li Xu | Zendy; Yan Li | Zendy; Yumei Wang | Zendy; Mingdian Tan | Zendy; Chao Huang | Zendy; Jinsong Li | Zendy; Ting C. Zhao | Zendy; Zhaoyuan Hou | Zendy; Naihe Jing | Zendy; Y. Eugene Chin | Zendy

Open Access

Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells

Author(s) -

Xiong-jun Wang,

Yunbo Qiao,

Minzhe M. Xiao,

Lingbo Wang,

Jun Chen,

Wenjian Lv,

Li Xu,

Yan Li,

Yumei Wang,

Mingdian Tan,

Chao Huang,

Jinsong Li,

Ting C. Zhao,

Zhaoyuan Hou,

Naihe Jing,

Y. Eugene Chin

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.12.081

Subject(s) - leukemia inhibitory factor receptor , microbiology and biotechnology , glycoprotein 130 , phosphorylation , stat3 , embryonic stem cell , stem cell , leukemia inhibitory factor , biology , chemistry , signal transduction , cytokine receptor , cellular differentiation , biochemistry , gene

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research