BMB Rep. 2016; 49(8): 437-442  
Critical role of protein L-isoaspartyl methyltransferase in basic fibroblast growth factor-mediated neuronal cell differentiation
To Thi Mai Dung1,#, Young-Su Yi1,2,#, Jieun Heo1, Woo Seok Yang1, Ji Hye Kim1, Han Gyung Kim1, Jae Gwang Park1, Byong Chul Yoo3, Jae Youl Cho1,* & Sungyoul Hong1,*
1Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, 2Department of Pharmaceutical Engineering, Cheongju University, Cheongju 28503, 3Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang 10408, Korea
Correspondence to: Jae Youl Cho, Tel: +82-31-290-7868; Fax: +82-31-290-7870; E-mail: jaecho@skku.edu, Sungyoul Hong, Tel: +82-31-290-7862; Fax: +82-31-290-7870; E-mail: syhong@skku.edu
Published online: August 31, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
We aimed to study the role of protein L-isoaspartyl methyltransferase (PIMT) in neuronal differentiation using basic fibroblast growth factor (bFGF)-induced neuronal differentiation, characterized by cell-body shrinkage, long neurite outgrowth, and expression of neuronal differentiation markers light and medium neurofilaments (NF). The bFGF-mediated neuronal differentiation of PC12 cells was induced through activation of mitogen-activated protein kinase (MAPK) signaling molecules [MAPK kinase 1/2 (MEK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2), and p90RSK], and phosphatidylinositide 3-kinase (PI3K)/Akt signaling molecules PI3Kp110β, PI3Kp110γ, Akt, and mTOR. Inhibitors (adenosine dialdehyde and S-adenosylhomocysteine) of protein methylation suppressed bFGF-mediated neuronal differentiation of PC12 cells. PIMTeficiency caused by PIMT-specific siRNA inhibited neuronal differentiation of PC12 cells by suppressing phosphorylation of MEK1/2 and ERK1/2 in the MAPK signaling pathway and Akt and mTOR in the PI3K/Akt signaling pathway. Therefore, these results suggested that PIMT was critical for bFGF-mediated neuronal differentiation of PC12 cells and regulated the MAPK and Akt signaling pathways.
Keywords: Akt, Basic fibroblast growth factor, Mitogen-activated protein kinase, Neuronal differentiation, Phosphatidylinositide 3-kinase, Protein L-isoaspartyl methyltransferase


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