title: Critical role of protein L-isoaspartyl methyltransferase in basic fibroblast growth factor-mediated neuronal cell differentiation.
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. [BMB Reports 2016; 49(8): 437-442].
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: To Thi Mai
authors.initials: TT
authors.lastname: Dung
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419; Department of Pharmaceutical Engineering, Cheongju University, Cheongju 28503, Korea.
authors.forename: Young-Su
authors.initials: YS
authors.lastname: Yi
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Heo
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Han Gyung
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Jae Gwang
authors.initials: JG
authors.lastname: Park
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang 10408, Korea.
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016222:Fibroblast Growth Factor 2; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases