Interferon γ (IFNγ) Signaling via Mechanistic Target of Rapamycin Complex 2 (mTORC2) and Regulatory Effects in the Generation of Type II Interferon Biological Responses
Open accessAbstract
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.
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No data exist on the in vivo outcomes of mTORi on IFN-γ signaling and function.
“Although the IFN-γ and the mTOR pathways seem to be tightly interwoven, no data exist on the in vivo outcomes of mTORi on IFN-γ signaling and function38–40.”
From Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation (2019) · cites this paper as [38]
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- Authors
- Kroczynska, B., Rafidi, R. L., Majchrzak-Kita, B., Kosciuczuk, E. M., Blyth, G. T., Jemielity, J., Warminska, Z., Saleiro, D., Mehrotra, S., Arslan, A. D., Fish, E. N., & Platanias, L. C.
- Affiliations
- Northwestern University (US)
- University Health Network (CA)
- University of Warsaw (PL)
- Corresponding author
- Platanias, Leonidas C.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 291
- Issue
- 5
- Pages
- 2389-2396
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4732221
- OpenAlex
- W2346942712
- Cited by
- 29
- References
- 55
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 8 · 2018: 4 · 2017: 1 · 2016: 3
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA77816, CA155566, CA161796)
- U.S. Department of Veterans Affairs (I01CX000916)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- interferon-gamma signaling, mTORC2, Rictor, Akt, mTORC1, eIF4F, interferon-gamma, interferon-stimulated genes, mRNA translation, antiviral response, antiproliferative response, hematopoiesis, interferon-gamma receptor
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Rapamycin-Insensitive Companion of mTOR Protein, Animals, Antiviral Agents, Carrier Proteins, Fibroblasts, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Humans, Interferon-gamma, Phosphorylation, Polyribosomes, Protein Biosynthesis, Signal Transduction, Receptors, Interferon, Mice, Knockout, U937 Cells, Eukaryotic Initiation Factor-4F, Multiprotein Complexes, Interferon-Stimulated Gene Factor 3, gamma Subunit, Mice, Chemokine CXCL10, TOR Serine-Threonine Kinases
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