PIKKing on PKB: regulation of PKB activity by phosphorylation
PIKKing on PKB: regulation of PKB activity by phosphorylation
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DOI：
10.1016/j.ceb.2009.02.002
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发表时间：
2009-04-01
影响因子：
7.5
通讯作者：
Hemmings, Brian A.
中科院分区：
文献类型：
--
作者：
Bozulic, Lana;Hemmings, Brian A.
Ser/Thr蛋白激酶PKB/Akt是一个重要的调节因子，参与细胞的生长、增殖和存活等过程。PKB显然是一种重要的信号分子，广泛的研究工作旨在了解其调节和作用。最近的研究疏水基序磷酸化的PKB活性的调节已经产生了一些令人兴奋的发现PI 3-激酶样激酶家族（PIKKs）的成员作为PKB调节剂。哺乳动物雷帕霉素靶蛋白复合物2（mTORC 2）和DNA依赖性蛋白激酶（DNA-PK）都可以磷酸化丝氨酸473并激活PKB。本文综述了mTORC 2和DNA-PK以刺激依赖性和环境依赖性的方式对PKB的调节，以及PKB活性、底物特异性和治疗干预的可能影响。
Ser/Thr protein kinase PKB/Akt is a key regulator of a wide range of cellular processes including growth, proliferation and survival. PKB is clearly a crucial signaling molecule and extensive research efforts aim to understand its regulation and action. Recent studies of the regulation of PKB activity by hydrophobic motif phosphorylation have yielded several exciting findings about members of the PI3-kinase-like family of kinases (PIKKs) acting as PKB regulators. Mammalian target of rapamycin complex 2 (mTORC2) and DNA-dependent protein kinase (DNA-PK) can both phosphorylate Ser473 and activate PKB. This present review concerns PKB regulation by mTORC2 and DNA-PK in a stimulus-dependent and context-de pendent manner and the possible implications of this for PKB activity, substrate specificity and therapeutic intervention.