Abstract
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.