RRC ID 71995
著者 Kitamura N, Fujiwara N, Hayakawa K, Ohama T, Sato K.
タイトル Protein phosphatase 6 promotes neurite outgrowth by promoting mTORC2 activity in N2a cells.
ジャーナル J Biochem
Abstract Understanding the molecular mechanism of neuronal differentiation is important to overcome the incurable diseases caused by nervous system damage. Neurite outgrowth is prerequisite for neuronal differentiation and regeneration, and cAMP response element-binding protein (CREB) is one of the major transcriptional factors positively regulating this process. Neuronal differentiation stimuli activate mammalian target of rapamycin (mTOR) complex 2 (mTORC2)/Akt signalling to phosphorylate CREB; however, the precise molecular mechanism of this event has not been fully understood. In this manuscript, we show that neuronal differentiation stimuli increased a protein level of protein phosphatase 6 (PP6), a member of type 2A Ser/Thr protein phosphatases. PP6 knockdown suppressed mTORC2/Akt/CREB signalling and results in failure of neurite outgrowth. SIN1 is a unique component of mTORC2 that enhances mTORC2 activity towards Akt when it is in dephosphorylated form. We found PP6 knockdown increased SIN1 phosphorylation. These data suggest that PP6 may positively regulate neurite outgrowth by dephosphorylating SIN1 to activate mTORC2/Akt/CREB signalling.
巻・号 170(1)
ページ 131-138
公開日 2021-9-22
DOI 10.1093/jb/mvab028
PII 6329266
PMID 34314486
MeSH Animals Cells, Cultured Humans Mechanistic Target of Rapamycin Complex 2 / metabolism* Mice Neuronal Outgrowth Phosphoprotein Phosphatases / metabolism*
IF 2.476
リソース情報
ヒト・動物細胞 MC3T3-G2/PA6(RCB1127)