Pim2 and Akt kinase regulation of mTORC1: TSC2 (forms a complex with TSC1) inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and 4EBP1 and the assembly of the elongation initiation factor 4E eIF4F complex comprising eIF4E, eIF4G, and eIF4A by negatively regulating mTORC1 signaling. TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. See the article by Lu et al beginning on page 1610 where it is reported that Pim2 directly phosphorylates TSC2 on Ser-1798 (relieving its suppression on RHEB in mTORC1; solid line) and far less efficiently phosphorylates PRAS40 (dotted line), leading to its release from mTORC1 (PRAS40 suppresses mTORC1 activation). In contrast, PRAS40 is the main effector of Akt, which phosphorylates TSC2 on Ser-939 and Thr-1462.