Department of Microbiology, Jeonbuk National University Medical School, Jeonju, Jeollabuk 54896, Republic of Korea.
Division of Anatomy and Developmental Biology, Department of Oral Biology, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea.
Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12070. Epub 2021 Apr 13.
Leukemia inhibitory factor (LIF) is a stem cell growth factor that maintains self‑renewal of mouse embryonic stem cells (mESCs). LIF is a cytokine in the interleukin‑6 family and signals via the common receptor subunit gp130 and ligand‑specific LIF receptor. LIF causes heterodimerization of the LIF receptor and gp130, activating the Janus kinase/STAT and MAPK pathways, resulting in changes in protein phosphorylation. The present study profiled LIF‑mediated protein phosphorylation changes in mESCs via proteomic analysis. mESCs treated in the presence or absence of LIF were analyzed via two‑dimensional differential in‑gel electrophoresis and protein and phosphoprotein staining. Protein identification was performed by matrix‑assisted laser desorption/ionization‑time of flight mass spectrophotometry. Increased phosphorylation of 16 proteins and decreased phosphorylation of 34 proteins in response to LIF treatment was detected. Gene Ontology terms enriched in these proteins included 'organonitrogen compound metabolic process', 'regulation of mRNA splicing via spliceosome' and 'nucleotide metabolic process'. The present results revealed that LIF modulated phosphorylation levels of nucleotide metabolism‑associated proteins, thus providing insight into the mechanism underlying LIF action in mESCs.
白血病抑制因子（LIF）是一种干细胞生长因子，可维持小鼠胚胎干细胞（mESC）的自我更新。LIF 是白细胞介素 6 家族中的一种细胞因子，通过共同受体亚基 gp130 和配体特异性 LIF 受体信号转导。LIF 导致 LIF 受体和 gp130 形成异二聚体，激活 Janus 激酶/STAT 和 MAPK 途径，导致蛋白质磷酸化的变化。本研究通过蛋白质组学分析对 LIF 介导的 mESC 中的蛋白质磷酸化变化进行了分析。通过二维差异凝胶电泳和蛋白质及磷酸化蛋白质染色分析了存在或不存在 LIF 处理的 mESC。通过基质辅助激光解吸/电离飞行时间质谱进行蛋白质鉴定。结果发现，LIF 处理后有 16 种蛋白质的磷酸化水平增加，34 种蛋白质的磷酸化水平降低。这些蛋白质中富含的基因本体术语包括“含氮有机化合物代谢过程”、“通过剪接体调节 mRNA 剪接”和“核苷酸代谢过程”。本研究结果表明，LIF 调节了核苷酸代谢相关蛋白的磷酸化水平，从而为 LIF 在 mESC 中的作用机制提供了深入的见解。
