Akt phosphorylation and regulation of transketolase is a nodal point for amino acid control of purine synthesis.
Akt phosphorylation and regulation of transketolase is a nodal point for amino acid control of purine synthesis.
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DOI：
10.1016/j.molcel.2014.05.028
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发表时间：
2014-07-17
期刊：
影响因子：
16
通讯作者：
Boss, Gerry R.
中科院分区：
文献类型：
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作者：
Saha, Arindam;Connelly, Stephen;Jiang, Jingjing;Zhuang, Shunhui;Amador, Deron T.;Phan, Tony;Pilz, Renate B.;Boss, Gerry R.
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway integrates environmental clues to regulate cell growth and survival. We showed previously that depriving cells of a single essential amino acid rapidly and reversibly arrests purine synthesis. Here we demonstrate that amino acids via mTORC2 and IκB kinase regulate Akt activity, and Akt association and phosphorylation of transketolase (TKT), a key enzyme of the non-oxidative pentose phosphate pathway (PPP). Akt phosphorylates TKT on Thr382, markedly enhancing enzyme activity and increasing carbon flow through the non-oxidative PPP, thereby increasing purine synthesis. Mice fed a lysine-deficient diet for two days show decreased Akt activity, TKT activity, and purine synthesis in multiple organs. These results provide a new mechanism whereby Akt coordinates amino acid availability with glucose utilization, purine synthesis, and RNA and DNA synthesis.
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影响因子：
4.8
作者：
Lu, Xin;Bennet, Bryson;Kang, Yibin
通讯作者：
Kang, Yibin
影响因子：
16
作者：
Comb, William C.;Hutti, Jessica E.;Baldwin, Albert S.
通讯作者：
Baldwin, Albert S.
影响因子：
29
作者：
Gulati, Pawan;Gaspers, Lawrence D.;Thomas, George
通讯作者：
Thomas, George
影响因子：
29
作者：
Hagiwara, Asami;Cornu, Marion;Hall, Michael N.
通讯作者：
Hall, Michael N.
DOI：
10.1038/nrm3522
发表时间：
2013-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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