Figures & data
Figure 1. Schematic depiction on exogenous LIF mediated intra-cellular signaling pathways for robust self-renewal in mESCs. LIF activates at least 3 intra-cellular signaling pathways: Jak-Stat3, PI3K-Akt and Shp2-MAPK pathways. Upon LIF stimulation, Jaks (Jak1, Jak2, Jak3 and Tyk2) are activated by auto-phosphorylation. Activated Jaks induce downstream cascades. Stat3 is phosphorylated and activated by Jaks, and subsequently induces the expressions of various pluripotent associated genes. Activated PI3K-Akt by Jaks also positively regulates the genes. In contrast to these 2 pathways, activated MAPK pathway inhibits the expressions of the pluripotency associated genes both at transcriptional and post-transcriptional levels. In addition to signal mediated transcriptional regulation, activated Jak2 tunes the chromatin status through histone modification. Also, activated Erk1 and Erk2 directly interact with Klf2 and phosphorylate it, leading to ubiquitination and degradion of Klf2 via proteasomal pathway. Also, LIF-PI3K-Akt axis stabilizes c-myc via inhibiting Gsk3 activity.
Figure 2. Comparison of LIF intra-cellular signaling activity in mESCs derived from permissive and non-permissive genetic backgrounds. Permissiveness for derivation and maintenance of mESCs is determined by the balance between Stat3 and MAPK pathways downstream of LIF.
