Department of Zoology, Cell Biology and Enzymology, Kakatiya University , Warangal , India.
Front Oncol. 2013 Jun 20;3:165. doi: 10.3389/fonc.2013.00165. eCollection 2013.
The serine threonine protein kinase, Akt, is at the central hub of signaling pathways that regulates cell growth, differentiation, and survival. The reciprocal relation that exists between the two activating phosphorylation sites of Akt, T308 and S473, and the two mTOR complexes, C1 and C2, forms the central controlling hub that regulates these cellular functions. In our previous review "PI3Kinase (PI3K)-AKT-mTOR and Wnt signaling pathways in cell cycle" we discussed the reciprocal relation between mTORC1 and C2 complexes in regulating cell metabolism and cell cycle progression in cancer cells. We present in this article, a hypothesis that activation of Akt-T308 phosphorylation in the presence of high ATP:AMP ratio promotes the stability of its phosphorylations and activates mTORC1 and the energy consuming biosynthetic processes. Depletion of energy leads to inactivation of mTORC1, activation of AMPK, FoxO, and promotes constitution of mTORC2 that leads to phosphorylation of Akt S473. Akt can also be activated independent of PI3K; this appears to have an advantage under situations like dietary restrictions, where insulin/insulin growth factor signaling could be a casualty.
丝氨酸苏氨酸蛋白激酶 Akt 处于调节细胞生长、分化和存活的信号通路的中心枢纽位置。Akt 的两个激活磷酸化位点 T308 和 S473 与两个 mTOR 复合物 C1 和 C2 之间存在相互关系，形成了调节这些细胞功能的中央控制枢纽。在我们之前的综述“PI3K（PI3K）-AKT-mTOR 和 Wnt 信号通路在细胞周期中”中，我们讨论了 mTORC1 和 C2 复合物在调节癌细胞代谢和细胞周期进展方面的相互关系。在本文中，我们提出了一个假设，即在高 ATP:AMP 比的情况下，Akt-T308 磷酸化的激活促进了其磷酸化的稳定性，并激活了 mTORC1 和能量消耗的生物合成过程。能量耗竭导致 mTORC1 失活，激活 AMPK、FoxO，并促进 mTORC2 的组成，导致 Akt S473 的磷酸化。Akt 也可以独立于 PI3K 激活；在饮食限制等情况下，这种情况似乎具有优势，因为胰岛素/胰岛素生长因子信号可能是一个牺牲品。
