title: Serine/threonine-protein kinase PFTK1 modulates oligodendrocyte differentiation via PI3K/AKT pathway.
abstract: 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.
authors.affiliation: College of Life Science and Technology, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, China.
authors.forename: Hai Jie
authors.initials: HJ
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Mian
authors.initials: M
authors.lastname: Wang
authors.forename: Shuang Ping
authors.initials: SP
authors.lastname: Ma
authors.forename: Bin Feng
authors.initials: BF
authors.lastname: Cheng
authors.forename: Zhi Chao
authors.initials: ZC
authors.lastname: Li
authors.forename: Zhi Wei
authors.initials: ZW
authors.lastname: Feng
mesh_terms: D000818:Animals; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D018844:Cyclin-Dependent Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C000603016:Cdk14 protein, rat