Serine/Threonine-Protein Kinase PFTK1 Modulates Oligodendrocyte Differentiation via PI3K/AKT Pathway

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• 作者：Hai Jie Yang (1)
  Lei Wang (1)
  Mian Wang (1)
  Shuang Ping Ma (1)
  Bin Feng Cheng (1)
  Zhi Chao Li (1)
  Zhi Wei Feng (1)
  
  1. College of Life Science and Technology ; Xinxiang Medical University ; 601 Jinsui Road ; Xinxiang ; Henan ; 453003 ; China
  
• 关键词：Oligodendrocyte ; Oligodendrocyte progenitor cell ; PFTK1 ; Differentiation ; Signaling pathway
• 刊名：Journal of Molecular Neuroscience
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：55
• 期：4
• 页码：977-984
• 全文大小：1,549 KB
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• 刊物主题：Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
• 出版者：Springer US
• ISSN：1559-1166

文摘

Oligodendrocytes (OLs) are derived oligodendrocyte progenitor cells (OPCs), and their differentiation is a tightly regulated process. It is known that cyclin-dependent kinases (CDKs) play an essential role as regulators of OPC differentiation. Here, we newly identified a CDK-like protein, PFTK1, to be involved in OPC differentiation. With serum-deprivation, OLN-93 undergoes OL differentiation, and PFTK1 expression is markedly decreased during differentiation. When PFTK1 is silenced, OL differentiation is potentiated, as suggested by the increase of various differentiation markers CNPase, MOG, CGT, and MBP, by qPCR and Western blotting analysis. Vice versa, PTTK1 overexpression has opposite effects on OL differentiation of OLN-93 in vitro. Next, the modulation mechanism underlying OL differentiation of OLN-93 was investigated. Significantly, PFTK1 silencing leads to the activation of PI3K/AKT pathway, but no activation of MAPK/ERK pathway. The inhibition of AKT by its specific inhibitor abrogates PFTK1 silencing-promoted OL differentiation, indicating that PFTK1 negatively regulates OL differentiation through PI3K/AKT pathway. Together, these findings indicate a novel role played by PFTK1 in OL development, thus presenting opportunities to establish therapeutic approaches in improving neurological recovery related to demyelinating disorders.