mTOR-rictor is the Ser473 kinase for AKT1 in mouse one-cell stage embryos

被引:18
作者
Zhang, Zhe [1 ,2 ]
Zhang, Guojun [3 ]
Xu, Xiaoyan [4 ]
Su, Wenhui [1 ]
Yu, Bingzhi [1 ]
机构
[1] China Med Univ, Dept Biochem & Mol Biol, Shenyang 110001, Liaoning Provin, Peoples R China
[2] China Med Univ, Hosp 1, Dept Urol, Shenyang 110001, Liaoning, Peoples R China
[3] China Med Univ, Shengjing Hosp, Dept Hematol, Shenyang 110001, Liaoning, Peoples R China
[4] China Med Univ, Coll Basic Med, Dept Pathophysiol, Shenyang 110001, Liaoning, Peoples R China
基金
中国国家自然科学基金;
关键词
Mouse; Embryo; mTOR; Raptor; Rictor; AKT1; shRNA; MAMMALIAN TARGET; SIGNALING PATHWAY; BINDING PARTNER; RAPAMYCIN; RAPTOR; PHOSPHORYLATION; TOR; GROWTH; ACTIVATION; SURVIVAL;
D O I
10.1007/s11010-011-1110-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mammalian target of rapamycin (mTOR) controls cell growth and proliferation via the raptor-mTOR (TORC1) and rictor-mTOR (TORC2) protein complexes. The mTORC2 containing mTOR and rictor is thought to be rapamycin insensitive and it is recently shown that both rictor and mTORC2 are essential for the development of both embryonic and extra embryonic tissues. To explore rictor function in the early development of mouse embryos, we disrupted the expression of rictor, a specific component of mTORC2, in mouse fertilized eggs by using rictor shRNA. Our results showed that one-cell stage eggs that were lack of rictor could not enter into the two-cell stage normally. Recent biochemical studies suggests that TORC2 is the elusive PDK2 (3'-phosphoinositide-dependent kinase 2) for AKT/PKB Ser473 phosphorylation, which is deemed necessary for AKT function, so we microinjected AKT-S473A into mouse fertilized eggs to investigate whether AKT-S473A is downstream effector of mTOR.rictor to regulate the mitotic division. Our findings revealed that the rictor induced phosphorylation of AKT in Ser473 is required for TORC2 function in early development of mouse embryos.
引用
收藏
页码:249 / 257
页数:9
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