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) |