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

Taichi Miura; Masahiko Kume; Takeshi Kawamura; Kazuo Yamamoto; Takao Hamakubo; Shoko Nishihara

doi:10.1016/j.stemcr.2017.11.007

Stem Cell Reports (Jan 2018)

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

Taichi Miura,
Masahiko Kume,
Takeshi Kawamura,
Kazuo Yamamoto,
Takao Hamakubo,
Shoko Nishihara

Affiliations

Taichi Miura: Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan; National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
Masahiko Kume: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
Takeshi Kawamura: Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Komaba 4-6-1, Meguro-ku, Tokyo 153-8904, Japan
Kazuo Yamamoto: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
Takao Hamakubo: Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Komaba 4-6-1, Meguro-ku, Tokyo 153-8904, Japan
Shoko Nishihara: Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan; Corresponding author

DOI: https://doi.org/10.1016/j.stemcr.2017.11.007
Journal volume & issue: Vol. 10, no. 1
pp. 272 – 286

Abstract

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Summary: 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 β-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 PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-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-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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