Figure 3.

Signaling pathways involved in pluripotency. (A) Wnt signaling pathway is stimulated via binding of Wnt proteins with frizzled receptors. This subsequently activates Dsh, which replaces GSK-3β from the Axin-APC complex, preventing degradation of β-catenin. Subsequently, β-catenin translocates into the nucleus where it associates with TCF/LEF proteins to activate transcription of Wnt target genes that cause self-renewal. (B) TGF-β signals through two main receptors, ie, the type II receptor and the Activin receptor. Upon activation, ligand-specific Smad proteins (Smad2/3) are phosphorylated and form a complex with Smad4, which translocates to the nucleus to activate gene expression. (C) The PI3K/Akt pathway is activated by IGF-1. Activation of PI3K activates Akt, which modulates the threshold of Smad2/3 activity and inhibits Erk and maintains GSK-3β activity, which in turn induces expression of Nanog. (D) The Jak/Stat signal pathway is principally initiated by LIF, which likewise initiates PI3K through which Akt and Erk are activated, ultimately resulting in upregulation of expression of Klf4 and Myc.

Abbreviations: Dsh, Dishevelled; LIF, leukemia inhibitory factor; LIFR, leukemia inhibitory factor receptor; TGF-β, transforming growth factor-beta; PI3K, phosphoinositide-3-kinase; GSK-3β, glycogen synthase kinase 3-beta; IGF-1, insulin-like growth factor-1.