O-GlcNAc on PKC? Inhibits the FGF4-PKC?-MEK-ERK1/2 Pathway via Inhibition of PKC? Phosphorylation in Mouse Embryonic Stem Cells.

ABSTRACT: Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). The FGF4-MEK-ERK1/2 pathway is inhibited to maintain ESCs in the undifferentiated state. However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized. O-linked ?-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. Here, we showed that the O-GlcNAc on the phosphorylation site of PKC? inhibits PKC? phosphorylation (activation) and, consequently, the FGF4-PKC?-MEK-ERK1/2 pathway in ESCs. Our results demonstrate the mechanism for the maintenance of the undifferentiated state of ESCs via the inhibition of the FGF4-PKC?-MEK-ERK1/2 pathway by O-GlcNAcylation on PKC?.

SUBMITTER: Miura T 

PROVIDER: S-EPMC5768893 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other