Bozulic Lana, Hemmings Brian A
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Curr Opin Cell Biol. 2009 Apr;21(2):256-61. doi: 10.1016/j.ceb.2009.02.002. Epub 2009 Mar 19.
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-dependent manner and the possible implications of this for PKB activity, substrate specificity and therapeutic intervention.
丝氨酸/苏氨酸蛋白激酶PKB/Akt是包括生长、增殖和存活在内的多种细胞过程的关键调节因子。PKB显然是一种关键的信号分子，大量研究致力于了解其调节和作用机制。最近关于通过疏水基序磷酸化调节PKB活性的研究，对作为PKB调节因子的PI3激酶样激酶家族（PIKKs）成员有了一些令人兴奋的发现。哺乳动物雷帕霉素靶蛋白复合物2（mTORC2）和DNA依赖性蛋白激酶（DNA-PK）都可以磷酸化Ser473并激活PKB。本综述关注mTORC2和DNA-PK以刺激依赖和背景依赖的方式对PKB的调节，以及这对PKB活性、底物特异性和治疗干预可能产生的影响。
