Intersection of mTOR and STAT signaling in immunity

Trends in Immunology

Volumn 36, Issue 1, 2015, Pages 21-29

  Saleiro, Diana ^a   Platanias, Leonidas C ^a,b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b JESSE BROWN VA MEDICAL CENTER   (United States)

Author keywords

Immunity; MTOR; Signaling; STAT

Indexed keywords

INTERFERON RECEPTOR; MAMMALIAN TARGET OF RAPAMYCIN; STAT PROTEIN; ALPHA BETA INTERFERON RECEPTOR; MULTIPROTEIN COMPLEX; PROTEIN BINDING; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 2;

ADAPTIVE IMMUNITY; CELL FATE; CELL FUNCTION; COMPLEX FORMATION; DENDRITIC CELL; DIFFERENTIATION; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; MACROPHAGE; PROTEIN INTERACTION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TRANSDUCER; ANIMAL; IMMUNITY; IMMUNOLOGY; METABOLISM; PHYSIOLOGY;

ANIMALS; DENDRITIC CELLS; HUMANS; IMMUNE SYSTEM; IMMUNITY; MACROPHAGES; MULTIPROTEIN COMPLEXES; PROTEIN BINDING; RECEPTOR, INTERFERON ALPHA-BETA; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; T-LYMPHOCYTES; TOR SERINE-THREONINE KINASES;

EID: 84919873454     PISSN: 14714906     EISSN: 14714981     Source Type: Journal    
DOI: 10.1016/j.it.2014.10.006     Document Type: Review

References (84)

1. Yang H., et al. Modulation of TSC-mTOR signaling on immune cells in immunity and autoimmunity. J. Cell. Physiol. 2014, 229:17-26.
2. Vainchenker W., Constantinescu S.N. JAK/STAT signaling in hematological malignancies. Oncogene 2013, 32:2601-2613.
3. Powell J.D., et al. Regulation of immune responses by mTOR. Annu. Rev. Immunol. 2012, 30:39-68.
4. Laplante M., Sabatini D.M. mTOR signaling in growth control and disease. Cell 2012, 149:274-293.
5. Beauchamp E.M., Platanias L.C. The evolution of the TOR pathway and its role in cancer. Oncogene 2013, 32:3923-3932.
6. Xu X., et al. mTOR, linking metabolism and immunity. Semin. Immunol. 2012, 24:429-435.
7. Yang K., Chi H. Tuning mTOR activity for immune balance. J. Clin. Invest. 2013, 123:5001-5004.
8. Benjamin D., et al. Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat. Rev. Drug Discov. 2011, 10:868-880.
9. Thoreen C.C., et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J. Biol. Chem. 2009, 284:8023-8032.
10. Feldman M.E., et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol. 2009, 7:e38.
11. Nelson V., et al. Next generation of mammalian target of rapamycin inhibitors for the treatment of cancer. Expert Opin. Investig. Drugs 2013, 22:715-722.
12. Altman J., et al. Dual mTORC2/mTORC1 targeting results in potent suppressive effects on acute myeloid leukemia (AML) progenitors. Clin. Cancer Res. 2011, 17:4378-4388.
13. Carayol N., et al. Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:12469-12474.
14. Janes M.R., et al. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat. Med. 2010, 16:205-213.
15. O'Shea J.J., et al. JAKs and STATs in immunity, immunodeficiency, and cancer. N. Engl. J. Med. 2013, 368:161-170.
16. O'Shea J.J., Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 2012, 36:542-550.
17. Stark G.R., Darnell J.E. The JAK-STAT pathway at twenty. Immunity 2012, 36:503-514.
18. Kaur S., et al. Critical roles for Rictor/Sin1 complexes in IFN-dependent gene transcription and generation of antiproliferative responses. J. Biol. Chem. 2014, 289:6581-6591.
19. + T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity 2010, 32:67-78.
20. Hand T.W., et al. Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:16601-16606.
21. Yamada O., et al. JAK-STAT and JAK-PI3K-mTORC1 pathways regulate telomerase transcriptionally and posttranslationally in ATL cells. Mol. Cancer Ther. 2012, 11:1112-1121.
22. Araki K., et al. mTOR regulates memory CD8 T-cell differentiation. Nature 2009, 460:108-112.
23. Chi H. Regulation and function of mTOR signaling in T cell fate decisions. Nat. Rev. Immunol. 2012, 12:325-338.
24. + T helper cell differentiation. Nat. Rev. Immunol. 2011, 11:239-250.
25. + T cells. Immunity 2011, 35:792-805.
26. Siegel A.M., et al. A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity 2011, 35:806-818.
27. Vahedi G., et al. STATs shape the active enhancer landscape of T cell populations. Cell 2012, 151:981-993.
28. Takada K., Jameson S.C. Naive T cell homeostasis: from awareness of space to a sense of place. Nat. Rev. Immunol. 2009, 9:823-832.
29. + T cell memory and tumor immunity. Immunity 2011, 34:541-553.
30. + T cell homeostasis. J. Immunol. 2003, 170:210-217.
31. + T cell responses. J. Immunol. 2010, 185:2116-2124.
32. Hand T.W., Kaech S.M. Intrinsic and extrinsic control of effector T cell survival and memory T cell development. Immunol. Res. 2009, 45:46-61.
33. + T cells in humans via recovering the phosphatidylinositol 3-kinase/AKT pathway. J. Immunol. 2007, 179:6734-6740.
34. + central memory T cells. J. Exp. Med. 2007, 204:79-91.
35. + T cells. Blood 2009, 113:6619-6628.
36. Wofford J.A., et al. IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival. Blood 2008, 111:2101-2111.
37. Delgoffe G.M., et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 2009, 30:832-844.
38. Delgoffe G.M., et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 2011, 12:295-303.
39. Linossi E.M., et al. Suppression of cytokine signaling: the SOCS perspective. Cytokine Growth Factor Rev. 2013, 24:241-248.
40. Yoshimura A., et al. SOCS proteins, cytokine signalling and immune regulation. Nat. Rev. Immunol. 2007, 7:454-465.
41. Lee K., et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 2010, 32:743-753.
42. Powell J.D., Delgoffe G.M. The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 2010, 33:301-311.
43. Park Y., et al. TSC1 regulates the balance between effector and regulatory T cells. J. Clin. Invest. 2013, 123:5165-5178.
44. + T cells. Clin. Immunol. 2013, 148:227-236.
45. + regulatory T-cell development in mice. FASEB J. 2013, 27:3979-3990.
46. Cohney S.J., et al. SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation. Mol. Cell. Biol. 1999, 19:4980-4988.
47. Geissmann F., et al. Development of monocytes, macrophages, and dendritic cells. Science 2010, 327:656-661.
48. van de Laar L., et al. Human CD34-derived myeloid dendritic cell development requires intact phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin signaling. J. Immunol. 2010, 184:6600-6611.
49. Wang Y., et al. Tuberous sclerosis 1 (Tsc1)-dependent metabolic checkpoint controls development of dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:E4894-E4903.
50. Wölfle S.J., et al. PD-L1 expression on tolerogenic APCs is controlled by STAT-3. Eur. J. Immunol. 2011, 41:413-424.
51. Sun Y., et al. Cutting edge: Negative regulation of dendritic cells through acetylation of the nonhistone protein STAT-3. J. Immunol. 2009, 182:5899-5903.
52. Ohtani M., et al. Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells. Blood 2008, 112:635-643.
53. Haidinger M., et al. A versatile role of mammalian target of rapamycin in human dendritic cell function and differentiation. J. Immunol. 2010, 185:3919-3931.
54. Weichhart T., et al. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 2008, 29:565-577.
55. Wang H., et al. Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-β-signaling pathways regulates the innate inflammatory response. J. Immunol. 2011, 186:5217-5226.
56. Rosborough B.R., et al. Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1, and regulatory T-cell induction. Blood 2013, 121:3619-3630.
57. Platanias L.C. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 2005, 5:375-386.
58. Ivashkiv L.B., Donlin L.T. Regulation of type I interferon responses. Nat. Rev. Immunol. 2014, 14:36-49.
59. Fish E.N., Platanias L.C. Interferon receptor signaling in malignancy: a network of cellular pathways defining biological outcomes. Mol. Cancer Res. 2014, Published online September 12, 2014, http://dx.doi.org/10.1158/1541-7786.MCR-14-0450.
60. Kaur S., et al. Regulatory effects of mTORC2 complexes in type I IFN signaling and in the generation of IFN responses. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:7723-7728.
61. Kaur S., et al. Regulatory effects of mammalian target of rapamycin-activated pathways in type I and II interferon signaling. J. Biol. Chem. 2007, 282:1757-1768.
62. Kaur S., et al. Role of the Akt pathway in mRNA translation of interferon-stimulated genes. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:4808-4813.
63. Tasian S.K., et al. Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia. Blood 2012, 120:833-842.
64. Bogani C., et al. mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms. PLoS ONE 2013, 8:e54826.
65. Gentzler R.D., et al. An overview of the mTOR pathway as a target in cancer therapy. Expert Opin. Ther. Targets 2012, 16:481-489.
66. Sancak Y., et al. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 2010, 141:290-303.
67. Bar-Peled L., et al. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell 2012, 150:1196-1208.
68. Bar-Peled L., et al. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 2013, 340:1100-1106.
69. Tsun Z.Y., et al. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol. Cell 2013, 52:495-505.
70. Efeyan A., et al. Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature 2013, 493:679-683.
71. Dibble C.C., et al. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol. Cell 2012, 47:535-546.
72. Laplante M., Sabatini D.M. Regulation of mTORC1 and its impact on gene expression at a glance. J. Cell Sci. 2013, 126:1713-1719.
73. Liu L., Parent C.A. Review series: TOR kinase complexes and cell migration. J. Cell Biol. 2011, 94:815-824.
74. Gan X., et al. Evidence for direct activation of mTORC2 kinase activity by phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 2011, 286:10998-11002.
75. Zinzalla V., et al. Activation of mTORC2 by association with the ribosome. Cell 2011, 144:757-768.
76. Toschi A., et al. Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: competition with rapamycin. Mol. Cell. Biol. 2009, 29:1411-1420.
77. Saci A., et al. Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size. Mol. Cell 2011, 42:50-61.
78. Ma X.M., Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell Biol. 2009, 10:307-318.
79. Chen C.H., et al. ER stress inhibits mTORC2 and Akt signaling through GSK-3β-mediated phosphorylation of rictor. Sci. Signal. 2011, 4:ra10.
80. Busch S., et al. mTOR mediates human trophoblast invasion through regulation of matrix-remodeling enzymes and is associated with serine phosphorylation of STAT3. Exp. Cell Res. 2009, 315:1724-1733.
81. Kim J.H., et al. Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. J. Biol. Chem. 2009, 284:35425-35432.
82. Fielhaber J.A., et al. Inhibition of mammalian target of rapamycin augments lipopolysaccharide-induced lung injury and apoptosis. J. Immunol. 2012, 188:4535-4542.
83. Kiu H., Nicholson S.E. Biology and significance of the JAK/STAT signaling pathways. Growth Factors 2012, 30:88-106.
84. Hervas-Stubbs S., et al. Direct effects of type I interferons on cells of the immune system. Clin. Cancer Res. 2011, 17:2619-2627.