Kroczynska Barbara, Rafidi Robert L, Majchrzak-Kita Beata, Kosciuczuk Ewa M, Blyth Gavin T, Jemielity Jacek, Warminska Zofia, Saleiro Diana, Mehrotra Swarna, Arslan Ahmet Dirim, Fish Eleanor N, Platanias Leonidas C
From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, the Department of Radiation Oncology, Northwestern University, Chicago, Illinois 60611.
From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
J Biol Chem. 2016 Jan 29;291(5):2389-96. doi: 10.1074/jbc.M115.664995. Epub 2015 Dec 8.
We provide evidence for a unique pathway engaged by the type II IFN receptor, involving mTORC2/AKT-mediated downstream regulation 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. Our studies establish that Rictor is essential for the generation of type II IFN-dependent antiviral and antiproliferative responses and that it controls the generation of type II IFN-suppressive effects on normal and malignant hematopoiesis. Together, our findings establish a central role for mTORC2 in IFNγ signaling and type II IFN responses.
我们提供了关于II型干扰素受体所参与的独特信号通路的证据，该通路涉及mTORC2/AKT介导的对mTORC1及其效应分子的下游调控。这些事件是真核翻译起始因子4F复合物（eIF4F）形成以及II型干扰素刺激基因的mRNA翻译起始所必需的。我们的研究表明，Rictor对于II型干扰素依赖性抗病毒和抗增殖反应的产生至关重要，并且它控制着II型干扰素对正常和恶性造血的抑制作用的产生。总之，我们的发现确立了mTORC2在IFNγ信号传导和II型干扰素反应中的核心作用。
