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Majoros A, Platanitis E, Kernbauer-Hölzl E, et al. Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses. Front Immunol. 2017;8:29doi: 10.3389/fimmu.2017.00029.
Majoros, A., Platanitis, E., Kernbauer-Hölzl, E., Rosebrock, F., Müller, M., & Decker, T. (2017). Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses. Frontiers in immunology, 829. https://doi.org/10.3389/fimmu.2017.00029
Majoros, Andrea, et al. "Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses." Frontiers in immunology vol. 8 (2017): 29. doi: https://doi.org/10.3389/fimmu.2017.00029
Majoros A, Platanitis E, Kernbauer-Hölzl E, Rosebrock F, Müller M, Decker T. Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses. Front Immunol. 2017 Jan 26;8:29. doi: 10.3389/fimmu.2017.00029. eCollection 2017. PMID: 28184222; PMCID: PMC5266721.
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Front Immunol. 2017 Jan 26;8:29. doi: 10.3389/fimmu.2017.00029. eCollection 2017.

Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses.

Frontiers in immunology

Andrea Majoros, Ekaterini Platanitis, Elisabeth Kernbauer-Hölzl, Felix Rosebrock, Mathias Müller, Thomas Decker

Affiliations

  1. Department of Microbiology, Immunobiology and Genetics, Max F. Perutz Laboratories, University of Vienna , Vienna , Austria.
  2. Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna , Vienna , Austria.

PMID: 28184222 PMCID: PMC5266721 DOI: 10.3389/fimmu.2017.00029

Abstract

Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK-STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1.

Keywords: JAK–STAT; innate immunity; interferon; non-canonical; signal transduction

References

  1. Nat Commun. 2014 Oct 16;5:5160 - PubMed
  2. Blood. 2011 Jul 28;118(4):1002-7 - PubMed
  3. Nat Rev Immunol. 2004 Jan;4(1):55-66 - PubMed
  4. J Biol Chem. 1999 Nov 5;274(45):32507-11 - PubMed
  5. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2849-54 - PubMed
  6. Immunol Rev. 2009 Mar;228(1):273-87 - PubMed
  7. Semin Immunol. 2015 Mar;27(2):85-101 - PubMed
  8. Virology. 2008 Oct 25;380(2):338-43 - PubMed
  9. Nat Rev Immunol. 2006 Nov;6(11):836-48 - PubMed
  10. J Biol Chem. 2008 Jul 4;283(27):18566-72 - PubMed
  11. Blood. 2016 Jun 23;127(25):3154-64 - PubMed
  12. Nature. 2015 Jan 1;517(7532):89-93 - PubMed
  13. Cell Host Microbe. 2016 Mar 9;19(3):375-87 - PubMed
  14. Science. 1993 Mar 19;259(5102):1739-42 - PubMed
  15. Nat Genet. 2012 Dec;44(12 ):1341-8 - PubMed
  16. J Immunol. 2001 May 15;166(10):6007-11 - PubMed
  17. Hepatology. 2013 Aug;58(2):603-16 - PubMed
  18. Mol Cell Biol. 2015 Jul;35(13):2332-43 - PubMed
  19. Mol Cell Biol. 2006 Nov;26(22):8562-71 - PubMed
  20. Brain. 2015 Oct;138(Pt 10):2834-46 - PubMed
  21. Exp Cell Res. 2006 Sep 10;312(15):2735-44 - PubMed
  22. J Immunol. 2010 Mar 15;184(6):3072-8 - PubMed
  23. Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13956-61 - PubMed
  24. Genes Immun. 2010 Jun;11(4):343-50 - PubMed
  25. Brain. 2011 Mar;134(Pt 3):693-703 - PubMed
  26. Nat Cell Biol. 2008 Apr;10(4):489-96 - PubMed
  27. Proc R Soc Lond B Biol Sci. 1957 Sep 12;147(927):258-67 - PubMed
  28. J Immunol. 2005 Sep 15;175(6):3946-54 - PubMed
  29. Annu Rev Med. 2015;66:311-28 - PubMed
  30. Oncoimmunology. 2015 May 26;4(11):e1047579 - PubMed
  31. JAKSTAT. 2013 Oct 1;2(4):e27521 - PubMed
  32. J Rheumatol. 2009 Aug;36(8):1631-8 - PubMed
  33. Cell Metab. 2012 Dec 5;16(6):814-24 - PubMed
  34. PLoS Pathog. 2013;9(11):e1003773 - PubMed
  35. JAKSTAT. 2013 Oct 1;2(4):e24860 - PubMed
  36. PLoS Pathog. 2011 Feb;7(2):e1001297 - PubMed
  37. BMC Genomics. 2010 Mar 25;11:199 - PubMed
  38. Immunity. 2006 Nov;25(5):745-55 - PubMed
  39. Oncogene. 2007 Jun 21;26(29):4253-60 - PubMed
  40. Immunity. 2005 Feb;22(2):247-57 - PubMed
  41. Blood. 2000 Jun 15;95(12):3891-9 - PubMed
  42. Immunol Rev. 2004 Dec;202:8-32 - PubMed
  43. Am J Hum Genet. 2005 Mar;76(3):528-37 - PubMed
  44. Immunity. 2000 Dec;13(6):795-804 - PubMed
  45. Cytokine Growth Factor Rev. 2016 Jun;29:71-81 - PubMed
  46. Immunity. 2003 Dec;19(6):793-802 - PubMed
  47. Immunity. 2012 Feb 24;36(2):166-74 - PubMed
  48. J Biol Chem. 1997 Feb 14;272(7):4600-5 - PubMed
  49. Basic Res Cardiol. 2013 Mar;108(2):326 - PubMed
  50. Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10213-8 - PubMed
  51. Immunol Rev. 2008 Oct;225:140-62 - PubMed
  52. Genes Dev. 2007 Jun 1;21(11):1396-408 - PubMed
  53. Biol Chem. 1999 Jun;380(6):699-703 - PubMed
  54. PLoS Biol. 2016 Oct 25;14 (10 ):e2000117 - PubMed
  55. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9373-8 - PubMed
  56. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5645-9 - PubMed
  57. Cell. 1992 Jul 24;70(2):313-22 - PubMed
  58. Biochimie. 2007 Jun-Jul;89(6-7):729-34 - PubMed
  59. Nat Rev Immunol. 2006 Aug;6(8):602-12 - PubMed
  60. J Biol Chem. 2003 Apr 11;278(15):13033-8 - PubMed
  61. J Exp Med. 2015 Sep 21;212(10):1641-62 - PubMed
  62. Nature. 2006 Dec 14;444(7121):860-7 - PubMed
  63. Blood. 2000 Mar 15;95(6):2076-83 - PubMed
  64. Oncoimmunology. 2016 May 19;5(9):e1186314 - PubMed
  65. J Leukoc Biol. 2004 Feb;75(2):163-89 - PubMed
  66. J Immunol. 2002 Aug 15;169(4):1665-8 - PubMed
  67. Neurology. 2012 Jul 31;79(5):406-11 - PubMed
  68. Proc Natl Acad Sci U S A. 2001 Jun 5;98 (12 ):6680-5 - PubMed
  69. J Allergy Clin Immunol. 2014 Mar;133(3):807-17 - PubMed
  70. Cancer Res. 2001 Sep 1;61(17):6540-7 - PubMed
  71. J Biol Chem. 2011 May 27;286(21):18731-46 - PubMed
  72. Cell. 1995 Jul 28;82(2):241-50 - PubMed
  73. J Biol Chem. 1999 Jan 22;274(4):1891-7 - PubMed
  74. Eur J Hum Genet. 2009 Oct;17(10):1309-13 - PubMed
  75. Immunity. 2000 Oct;13(4):561-71 - PubMed
  76. EMBO J. 2013 Oct 16;32(20):2751-63 - PubMed
  77. J Clin Immunol. 2009 Nov;29(6):815-25 - PubMed
  78. Science. 2009 Jun 26;324(5935):1713-6 - PubMed
  79. J Biol Chem. 1996 Aug 23;271(34):20494-500 - PubMed
  80. J Exp Med. 2007 May 14;204(5):987-94 - PubMed
  81. Trends Cell Biol. 2012 Aug;22(8):429-37 - PubMed
  82. Science. 1997 Nov 14;278(5341):1309-12 - PubMed
  83. J Exp Med. 2005 May 16;201(10):1543-53 - PubMed
  84. J Immunol. 2006 Oct 1;177(7):4530-40 - PubMed
  85. PLoS One. 2015 Dec 21;10 (12 ):e0144444 - PubMed
  86. Immunity. 2001 Jun;14(6):661-4 - PubMed
  87. Cell Metab. 2008 Jan;7(1):86-94 - PubMed
  88. Cytokine Growth Factor Rev. 2016 Jun;29:35-43 - PubMed
  89. Nat Rev Drug Discov. 2007 Dec;6(12):975-90 - PubMed
  90. Nat Immunol. 2003 Jan;4(1):69-77 - PubMed
  91. Nat Genet. 2010 Jan;42(1):68-71 - PubMed
  92. Nat Genet. 2010 Dec;42(12):1118-25 - PubMed
  93. Curr Opin Immunol. 2015 Feb;32:90-105 - PubMed
  94. J Immunol. 1998 Nov 1;161(9):4736-44 - PubMed
  95. Blood. 2006 Nov 15;108(10 ):3237-44 - PubMed
  96. Curr Opin Genet Dev. 2008 Oct;18(5):455-60 - PubMed
  97. Nat Rev Immunol. 2013 Nov;13(11):777-89 - PubMed
  98. J Immunol. 2015 Jul 1;195(1):210-6 - PubMed
  99. Nat Rev Mol Cell Biol. 2002 Sep;3(9):651-62 - PubMed
  100. J Immunol. 2002 Dec 1;169(11):6522-9 - PubMed
  101. Nat Rev Immunol. 2012 Apr 25;12(5):367-82 - PubMed
  102. JAKSTAT. 2013 Oct 1;2(4):e25666 - PubMed
  103. J Rheumatol. 2010 Mar;37(3):676-7; author reply 678 - PubMed
  104. J Exp Med. 2016 Nov 14;213(12 ):2527-2538 - PubMed
  105. Cell. 2016 Jan 28;164(3):564-78 - PubMed
  106. EMBO J. 2003 Feb 3;22(3):537-47 - PubMed
  107. Blood. 2014 Jan 23;123(4):520-9 - PubMed
  108. J Immunol. 2013 Mar 1;190(5):2335-44 - PubMed
  109. J Biol Chem. 1997 Aug 8;272(32):20070-6 - PubMed
  110. Immunity. 2000 Oct;13(4):549-60 - PubMed
  111. EMBO J. 2016 Mar 15;35(6):580-94 - PubMed
  112. Am J Physiol Endocrinol Metab. 2013 Aug 15;305(4):E485-95 - PubMed
  113. Science. 2009 Feb 6;323(5915):793-7 - PubMed
  114. Dev Growth Differ. 2011 May;53(4):548-57 - PubMed
  115. Cell Res. 2013 May;23(5):673-90 - PubMed
  116. Exp Cell Res. 2002 Jan 1;272(1):45-55 - PubMed
  117. Annu Rev Immunol. 1997;15:563-91 - PubMed
  118. Cancer Res. 2009 Apr 15;69(8):3673-80 - PubMed
  119. Hum Immunol. 2013 Jan;74(1):93-7 - PubMed
  120. Hepatology. 2014 Mar;59(3):870-85 - PubMed
  121. EMBO J. 1991 Apr;10(4):927-32 - PubMed
  122. Annu Rev Immunol. 1997;15:749-95 - PubMed
  123. Science. 1993 Mar 19;259(5102):1742-5 - PubMed
  124. J Virol. 1999 Jan;73(1):783-6 - PubMed
  125. J Immunol. 2007 Mar 1;178(5):3126-33 - PubMed
  126. JAKSTAT. 2013 Jan 1;2(1):e23820 - PubMed
  127. Hypertension. 2014 Apr;63(4):713-22 - PubMed
  128. EMBO J. 2016 Mar 15;35(6):555-7 - PubMed
  129. J Neurosci. 2014 Sep 3;34(36):11897-912 - PubMed
  130. J Immunol. 2011 Feb 1;186(3):1685-93 - PubMed
  131. PLoS One. 2012;7(6):e39141 - PubMed
  132. Endocr Relat Cancer. 2013 Aug 23;20(5):677-89 - PubMed
  133. J Cell Biol. 2004 Jun 21;165(6):823-33 - PubMed
  134. Annu Rev Immunol. 2014;32:513-45 - PubMed
  135. Rheumatology (Oxford). 2007 Jun;46(6):927-30 - PubMed
  136. Front Biosci (Landmark Ed). 2011 Jun 01;16:3214-32 - PubMed
  137. Cell. 1998 May 1;93(3):385-95 - PubMed
  138. Science. 1997 Nov 28;278(5343):1630-2 - PubMed
  139. Eur J Hum Genet. 2010 Apr;18(4):502-4 - PubMed
  140. Curr Opin Immunol. 2012 Aug;24(4):364-78 - PubMed
  141. Nat Rev Immunol. 2005 Sep;5(9):675-87 - PubMed
  142. EMBO J. 2000 Aug 1;19(15):4111-22 - PubMed
  143. Mol Cell. 2001 Dec;8(6):1327-38 - PubMed
  144. Am J Hum Genet. 2009 Mar;84(3):399-405 - PubMed
  145. Nat Immunol. 2009 Jun;10(6):587-94 - PubMed
  146. Nat Genet. 2012 Oct;44(10):1137-41 - PubMed
  147. Nat Immunol. 2014 Feb;15(2):168-76 - PubMed
  148. Immunity. 2012 Apr 20;36(4):515-28 - PubMed
  149. J Biol Chem. 2003 Aug 8;278(32):30091-7 - PubMed
  150. Am J Physiol Cell Physiol. 2012 Mar 1;302(5):C804-20 - PubMed
  151. Immunity. 2013 Feb 21;38(2):250-62 - PubMed
  152. EMBO Rep. 2016 Mar;17 (3):367-82 - PubMed
  153. J Biol Chem. 2009 Oct 30;284(44):30058-66 - PubMed
  154. Nat Rev Immunol. 2015 Jul;15(7):429-40 - PubMed
  155. Blood. 2003 Nov 1;102(9):3311-3 - PubMed
  156. Hypertension. 2014 Jan;63(1):119-27 - PubMed
  157. Cell. 1998 May 1;93(3):397-409 - PubMed
  158. J Exp Med. 2010 Sep 27;207(10):2053-63 - PubMed
  159. J Exp Med. 1993 Nov 1;178(5):1655-63 - PubMed
  160. Cell Rep. 2013 Aug 15;4(3):437-44 - PubMed
  161. J Interferon Cytokine Res. 2010 Aug;30(8):555-64 - PubMed

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