AKT phosphorylates TSC2, inhibiting it

AKT phosphorylates and inhibits TSC2 (tuberin), a suppressor of the TOR kinase pathway, which senses nutrient levels in the environment. TSC2 forms a protein complex with TSC1 and this complex acts as a GAP (GTPase activating protein) for the RHEB G-protein. RHEB, in turn, activates the TOR kinase. Thus, an active AKT1 activates the TOR kinase, both of which are positive signals for cell growth (an increase in cell mass) and division.<br>The TOR kinase regulates two major processes: translation of selected mRNAs in the cell and autophagy. In the presence of high nutrient levels TOR is active and phosphorylates the 4EBP protein releasing the eukaryotic initiation factor 4E (eIF4E), which is essential for cap-dependent initiation of translation and promoting growth of the cell (PMID: 15314020). TOR also phosphorylates the S6 kinase, which is implicated in ribosome biogenesis as well as in the modification of the S6 ribosomal protein. AKT can also activate mTOR by another mechanism, involving phosphorylation of PRAS40, an inhibitor of mTOR activity.

AKT（丝氨酸/苏氨酸激酶）通过磷酸化并抑制TSC2（管蛋白）来发挥作用，而TSC2是TOR激酶途径的抑制因子，该途径能够感知环境中的营养水平。TSC2与TSC1形成蛋白复合物，该复合物充当RHEB G蛋白的GTP酶活化蛋白（GAP）。RHEB进而激活TOR激酶。因此，活跃的AKT1激活TOR激酶，这两者均为细胞生长（细胞质量的增加）和分裂的积极信号。<br>TOR激酶调控两个主要过程：细胞中选定mRNA的翻译和自噬。在高营养水平存在的情况下，TOR处于活跃状态，并磷酸化4EBP蛋白，释放出真核起始因子4E（eIF4E），这对于帽依赖性翻译起始是必不可少的，并促进细胞生长（PMID: 15314020）。TOR还磷酸化S6激酶，S6激酶参与核糖体生物发生以及S6核糖体蛋白的修饰。AKT还可以通过另一种机制激活mTOR，该机制涉及PRAS40（mTOR活性的抑制剂）的磷酸化。