Interferon γ (IFNγ) Signaling via Mechanistic Target of Rapamycin Complex 2 (mTORC2) and Regulatory Effects in the Generation of Type II Interferon Biological Responses.

Abstract We provide evidence for a unique pathway engaged by the Type II IFN-receptor, involving mTORC2/AKT-mediated downstream regula-tion of mTORC1 and effectors. These events are required for formation of the eukaryotic translation initiation factor 4F complex (eIF4F) and initiation of mRNA translation of Type II interferon stimulated genes (ISGs). Our studies establish that Rictor is essential for the generation of Type II IFN-dependent antiviral and antiproliferative responses and controls the generation of Type II IFN-suppressive effects on normal and malignant hematopoiesis. Altogether, our findings establish a central role for mTORC2 in IFNγ-signaling and Type II IFN responses.