Model for the molecular mechanism of PKCs regulating self-renewal or differentiation in hPS cells.

<p>Our study suggested a model that FGF-2 activates PI3K/AKT, MEK/ERK-1/2, and PKCε/δ/ζ. PKCε, δ, and ζ inactivates directly or indirectly GSK-3β by phosphorylation which promotes differentiation of hPS cells. PKCε and ζ activates ERK-1/2 which promotes differentiation of hPS cells. Activin A activates SMAD-2/3 which controls self-renewal and differentiation while activin A together with FGF-2 activates both ERK-1/2 and PKCs. Inhibition of both ERK-1/2 and PKCs pathway provides a metastable undifferentiated state of hPS cells. Blue arrow indicated pathway promoting hPS cell self-renewal and black arrow indicated pathway promoting hPS cell differentiation.