title: 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 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.
authors.affiliation: 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.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kroczynska
authors.affiliation: From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Rafidi
authors.affiliation: the Toronto General Research Institute, University Health Network, and Department of Immunology, University of Toronto, Toronto, Ontario M5G 2MI, Canada.
authors.forename: Beata
authors.initials: B
authors.lastname: Majchrzak-Kita
authors.affiliation: From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, the Division of Hematology-Oncology, Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Kosciuczuk
authors.affiliation: From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Gavin T
authors.initials: GT
authors.lastname: Blyth
authors.affiliation: the Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland, and.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jemielity
authors.affiliation: the Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland, and the College of Inter-Faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, 02-089 Warsaw, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Warminska
authors.affiliation: From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Diana
authors.initials: D
authors.lastname: Saleiro
authors.affiliation: From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Swarna
authors.initials: S
authors.lastname: Mehrotra
authors.affiliation: From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Ahmet Dirim
authors.initials: AD
authors.lastname: Arslan
authors.affiliation: the Toronto General Research Institute, University Health Network, and Department of Immunology, University of Toronto, Toronto, Ontario M5G 2MI, Canada.
authors.forename: Eleanor N
authors.initials: EN
authors.lastname: Fish
authors.affiliation: From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, the Division of Hematology-Oncology, Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612, l-platanias@northwestern.edu.
authors.forename: Leonidas C
authors.initials: LC
authors.lastname: Platanias
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000378:metabolism; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D017471:Receptors, Interferon / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D000998:Antiviral Agents; D002352:Carrier Proteins; D054357:Chemokine CXCL10; D039562:Eukaryotic Initiation Factor-4F; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D007371:Interferon-gamma; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D017471:Receptors, Interferon; D058570:TOR Serine-Threonine Kinases; C485433:Cxcl10 protein, mouse; C120411:interferon receptor, type II; C525637:rictor protein, mouse; C494228:Isgf3g protein, mouse
keywords: PI3K; antiviral agent; interferon; signal transduction; translation control; translation initiation factor