STAT1β is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity

Molecular and Cellular Biology

Volumn 34, Issue 12, 2014, Pages 2235-2248

  Semper, Christian ^a   Leitner, Nicole R ^a   Lassnig, Caroline ^a   Parrini, Matthias ^a   Mahlakõiv, Tanel ^b,c   Rammerstorfer, Michael ^a   Lorenz, Karin ^a   Rigler, Doris ^a   Müller, Simone ^a   Kolbe, Thomas ^a,d   Vogl, Claus ^a   Rülicke, Thomas ^a   Staeheli, Peter ^b   Decker, Thomas ^e   Müller, Mathias ^a   Strobl, Birgit ^a  

^a UNIVERSITY OF VETERINARY MEDICINE   (Austria)

^b UNIVERSITY OF FREIBURG   (Germany)

^c UNIVERSITY OF FREIBURG   (Germany)

^d UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES   (Austria)

^e UNIVERSITY OF VIENNA   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; RECOMBINANT BETA INTERFERON; RECOMBINANT GAMMA INTERFERON; RNA; STAT1 PROTEIN; STAT1BETA PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTERIAL LOAD; BONE MARROW CELL; CONTROLLED STUDY; CYTOMEGALOVIRUS; ENCEPHALOMYOCARDITIS VIRUS; GENE EXPRESSION PROFILING; GENOTYPE; INNATE IMMUNITY; LISTERIA MONOCYTOGENES; MICROARRAY ANALYSIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN PHOSPHORYLATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SOUTHERN BLOTTING; SPLEEN; VESICULAR STOMATITIS VIRUS; VIRUS INFECTION; WESTERN BLOTTING;

ANIMALS; CELL NUCLEUS; GENE EXPRESSION REGULATION; GENE KNOCK-IN TECHNIQUES; GENES, DOMINANT; HERPESVIRIDAE INFECTIONS; IMMUNITY, INNATE; INTERFERON-BETA; INTERFERON-GAMMA; LISTERIA; LISTERIOSIS; MICE; MUROMEGALOVIRUS; PHOSPHORYLATION; PHOSPHOTYROSINE; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTEIN ISOFORMS; PROTEIN TRANSPORT; STAT1 TRANSCRIPTION FACTOR; TRANSCRIPTION, GENETIC;

EID: 84901360937     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.00295-14     Document Type: Article

References (72)

1. Levy DE, Darnell JE, Jr. 2002. Stats: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 3:651-662. http://dx.doi.org/10.1038/nrm909.
2. Bancerek J, Poss ZC, Steinparzer I, Sedlyarov V, Pfaffenwimmer T, Mikulic I, Dolken L, Strobl B, Muller M, Taatjes DJ, Kovarik P. 2013. CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity 38:250-262. http://dx.doi.org/10.1016/j.immuni.2012.10.017.
3. Sadzak I, Schiff M, Gattermeier I, Glinitzer R, Sauer I, Saalmuller A, Yang E, Schaljo B, Kovarik P. 2008. Recruitment of Stat1 to chromatin is required for interferon-induced serine phosphorylation of Stat1 transactivation domain. Proc. Natl. Acad. Sci. U. S. A. 105:8944-8949. http://dx.doi.org/10.1073/pnas.0801794105.
4. Varinou L, Ramsauer K, Karaghiosoff M, Kolbe T, Pfeffer K, Muller M, Decker T. 2003. Phosphorylation of the Stat1 transactivation domain is required for full-fledged IFN-gamma-dependent innate immunity. Immunity 19:793-802. http://dx.doi.org/10.1016/S1074-7613(03)00322-4.
5. Wen Z, Zhong Z, Darnell JE, Jr. 1995. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82:241-250. http://dx.doi.org/10.1016/0092-8674(95)90311-9.
6. Boisson-Dupuis S, Kong XF, Okada S, Cypowyj S, Puel A, Abel L, Casanova JL. 2012. Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes. Curr. Opin. Immunol. 24:364-378. http://dx.doi.org/10.1016/j.coi.2012.04.011.
7. Durbin JE, Hackenmiller R, Simon MC, Levy DE. 1996. Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell 84:443-450. http://dx.doi.org/10.1016/S0092-8674(00)81289-1.
8. Meraz MA, White JM, Sheehan KC, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenlund AC, Campbell D, Carver-Moore K, DuBois RN, Clark R, Aguet M, Schreiber RD. 1996. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84:431-442. http://dx.doi.org/10.1016/S0092-8674(00)81288-X.
9. Muller M, Laxton C, Briscoe J, Schindler C, Improta T, Darnell JE, Jr, Stark GR, Kerr IM. 1993. Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon-alpha and -gamma signal transduction pathways. EMBO J. 12:4221-4228.
10. Shuai K, Stark GR, Kerr IM, Darnell JE, Jr. 1993. A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science 261:1744-1746. http://dx.doi.org/10.1126/science.7690989.
11. Zakharova N, Lymar ES, Yang E, Malik S, Zhang JJ, Roeder RG, Darnell JE, Jr. 2003. Distinct transcriptional activation functions of STAT1alpha and STAT1beta on DNA and chromatin templates. J. Biol. Chem. 278:43067-43073. http://dx.doi.org/10.1074/jbc.M308166200.
12. Schindler C, Darnell JE, Jr. 1995. Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu. Rev. Biochem. 64:621-651. http://dx.doi.org/10.1146/annurev.bi.64.070195.003201.
13. Vinkemeier U, Cohen SL, Moarefi I, Chait BT, Kuriyan J, Darnell JE, Jr. 1996. DNA binding of in vitro activated Stat1 alpha, Stat1 beta and truncated Stat1: interaction between NH2-terminal domains stabilizes binding of two dimers to tandem DNA sites. EMBO J. 15:5616-5626.
14. Bhattacharya S, Eckner R, Grossman S, Oldread E, Arany Z, D'Andrea A, Livingston DM. 1996. Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha. Nature 383:344-347. http://dx.doi.org/10.1038/383344a0.
15. Qureshi SA, Leung S, Kerr IM, Stark GR, Darnell JE, Jr. 1996. Function of Stat2 protein in transcriptional activation by alpha interferon. Mol. Cell. Biol. 16:288-293.
16. Baran-Marszak F, Feuillard J, Najjar I, Le Clorennec C, Bechet JM, Dusanter-Fourt I, Bornkamm GW, Raphael M, Fagard R. 2004. Differential roles of STAT1alpha and STAT1beta in fludarabine-induced cell cycle arrest and apoptosis in human B cells. Blood 104:2475-2483. http://dx.doi.org/10.1182/blood-2003-10-3508.
17. Alvarez GR, Zwilling BS, Lafuse WP. 2003. Mycobacterium avium inhibition of IFN-gamma signaling in mouse macrophages: Toll-like receptor 2 stimulation increases expression of dominant-negative STAT1 beta by mRNA stabilization. J. Immunol. 171:6766-6773.
18. Bhardwaj N, Rosas LE, Lafuse WP, Satoskar AR. 2005. Leishmania inhibits STAT1-mediated IFN-gamma signaling in macrophages: increased tyrosine phosphorylation of dominant negative STAT1beta by Leishmania mexicana. Int. J. Parasitol. 35:75-82. http://dx.doi.org/10.1016/j.ijpara.2004.10.018.
19. Ruvolo V, Navarro L, Sample CE, David M, Sung S, Swaminathan S. 2003. The Epstein-Barr virus SM protein induces STAT1 and interferonstimulated gene expression. J. Virol. 77:3690-3701. http://dx.doi.org/10.1128/JVI.77.6.3690-3701.2003.
20. Mamo S, Kobolak J, Borbiro I, Biro T, Bock I, Dinnyes A. 2010. Gene targeting and calcium handling efficiencies in mouse embryonic stem cell lines. World J. Stem Cells 2:127-140. http://dx.doi.org/10.4252/wjsc.v2.i6.127.
21. Schwenk F, Baron U, Rajewsky K. 1995. A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. Nucleic Acids Res. 23:5080-5081. http://dx.doi.org/10.1093/nar/23.24.5080.
22. Teppner I, Aigner B, Schreiner E, Muller M, Windisch M. 2004. Polymorphic microsatellite markers in the outbred CFW and ICR stocks for the generation of speed congenic mice on C57BL/6 background. Lab Anim. 38:406-412. http://dx.doi.org/10.1258/0023677041958882.
23. Karaghiosoff M, Neubauer H, Lassnig C, Kovarik P, Schindler H, Pircher H, McCoy B, Bogdan C, Decker T, Brem G, Pfeffer K, Muller M. 2000. Partial impairment of cytokine responses in Tyk2-deficient mice. Immunity 13:549-560. http://dx.doi.org/10.1016/S1074-7613(00)00054-6.
24. Strobl B, Bubic I, Bruns U, Steinborn R, Lajko R, Kolbe T, Karaghiosoff M, Kalinke U, Jonjic S, Muller M. 2005. Novel functions of tyrosine kinase 2 in the antiviral defense against murine cytomegalovirus. J. Immunol. 175:4000-4008.
25. Kovarik P, Stoiber D, Novy M, Decker T. 1998. Stat1 combines signals derived from IFN-gamma and LPS receptors during macrophage activation. EMBO J. 17:3660-3668. http://dx.doi.org/10.1093/emboj/17.13.3660.
26. Nissen RM, Yamamoto KR. 2000. The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev. 14:2314-2329. http://dx.doi.org/10.1101/gad.827900.
27. Leitner NR, Strobl B, Bokor M, Painz R, Kolbe T, Rulicke T, Muller M, Karaghiosoff M. 2006. A time- and dose-dependent STAT1 expression system. BMC Biotechnol. 6:48. http://dx.doi.org/10.1186/1472-6750-6-48.
28. Stockinger S, Reutterer B, Schaljo B, Schellack C, Brunner S, Materna T, Yamamoto M, Akira S, Taniguchi T, Murray PJ, Muller M, Decker T. 2004. IFN regulatory factor 3-dependent induction of type I IFNs by intracellular bacteria is mediated by a TLR- and Nod2-independent mechanism. J. Immunol. 173:7416-7425.
29. Prchal-Murphy M, Semper C, Lassnig C, Wallner B, Gausterer C, Teppner-Klymiuk I, Kobolak J, Muller S, Kolbe T, Karaghiosoff M, Dinnyes A, Rulicke T, Leitner NR, Strobl B, Muller M. 2012. TYK2 kinase activity is required for functional type I interferon responses in vivo. PLoS One 7:e39141. http://dx.doi.org/10.1371/journal.pone.0039141.
30. Pott J, Mahlakoiv T, Mordstein M, Duerr CU, Michiels T, Stockinger S, Staeheli P, Hornef MW. 2011. IFN-lambda determines the intestinal epithelial antiviral host defense. Proc. Natl. Acad. Sci. U. S. A. 108:7944-7949. http://dx.doi.org/10.1073/pnas.1100552108.
31. Maritano D, Sugrue ML, Tininini S, Dewilde S, Strobl B, Fu X, Murray-Tait V, Chiarle R, Poli V. 2004. The STAT3 isoforms alpha and beta have unique and specific functions. Nat. Immunol. 5:401-409. http://dx.doi.org/10.1038/ni1052.
32. Gough DJ, Messina NL, Hii L, Gould JA, Sabapathy K, Robertson AP, Trapani JA, Levy DE, Hertzog PJ, Clarke CJ, Johnstone RW. 2010. Functional crosstalk between type I and II interferon through the regulated expression of STAT1. PLoS Biol. 8:e1000361. http://dx.doi.org/10.1371/journal.pbio.1000361.
33. Rusinova I, Forster S, Yu S, Kannan A, Masse M, Cumming H, Chapman R, Hertzog PJ. 2013. Interferome v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Res. 41:D1040-D1046. http://dx.doi.org/10.1093/nar/gks1215.
34. Wong LH, Sim H, Chatterjee-Kishore M, Hatzinisiriou I, Devenish RJ, Stark G, Ralph SJ. 2002. Isolation and characterization of a human STAT1 gene regulatory element. Inducibility by interferon (IFN) types I and II and role of IFN regulatory factor-1. J. Biol. Chem. 277:19408-19417. http://dx.doi.org/10.1074/jbc.M111302200.
35. Ramsauer K, Farlik M, Zupkovitz G, Seiser C, Kroger A, Hauser H, Decker T. 2007. Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene. Proc. Natl. Acad. Sci. U. S. A. 104:2849-2854. http://dx.doi.org/10.1073/pnas.0610944104.
36. Chen LS, Wei PC, Liu T, Kao CH, Pai LM, Lee CK. 2009. STAT2 hypomorphic mutant mice display impaired dendritic cell development and antiviral response. J. Biomed. Sci. 16:22. http://dx.doi.org/10.1186/1423-0127-16-22.
37. Detje CN, Meyer T, Schmidt H, Kreuz D, Rose JK, Bechmann I, Prinz M, Kalinke U. 2009. Local type I IFN receptor signaling protects against virus spread within the central nervous system. J. Immunol. 182:2297-2304. http://dx.doi.org/10.4049/jimmunol.0800596.
38. Fensterl V, Wetzel JL, Ramachandran S, Ogino T, Stohlman SA, Bergmann CC, Diamond MS, Virgin HW, Sen GC. 2012. Interferon-induced Ifit2/ISG54 protects mice from lethal VSV neuropathogenesis. PLoS Pathog. 8:e1002712. http://dx.doi.org/10.1371/journal.ppat.1002712.
39. Mordstein M, Kochs G, Dumoutier L, Renauld JC, Paludan SR, Klucher K, Staeheli P. 2008. Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathog. 4:e1000151. http://dx.doi.org/10.1371/journal.ppat.1000151.
40. Mordstein M, Neugebauer E, Ditt V, Jessen B, Rieger T, Falcone V, Sorgeloos F, Ehl S, Mayer D, Kochs G, Schwemmle M, Gunther S, Drosten C, Michiels T, Staeheli P. 2010. Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections. J. Virol. 84:5670-5677. http://dx.doi.org/10.1128/JVI.00272-10.
41. Grimm D, Staeheli P, Hufbauer M, Koerner I, Martinez-Sobrido L, Solorzano A, Garcia-Sastre A, Haller O, Kochs G. 2007. Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc. Natl. Acad. Sci. U. S. A. 104:6806-6811. http://dx.doi.org/10.1073/pnas.0701849104.
42. Kochs G, Koerner I, Thiel L, Kothlow S, Kaspers B, Ruggli N, Summerfield A, Pavlovic J, Stech J, Staeheli P. 2007. Properties of H7N7 influenza A virus strain SC35M lacking interferon antagonist NS1 in mice and chickens. J. Gen. Virol. 88:1403-1409. http://dx.doi.org/10.1099/vir.0.82764-0.
43. Gil MP, Salomon R, Louten J, Biron CA. 2006. Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo. Blood 107:987-993. http://dx.doi.org/10.1182/blood-2005-07-2834.
44. Kernbauer E, Maier V, Stoiber D, Strobl B, Schneckenleithner C, Sexl V, Reichart U, Reizis B, Kalinke U, Jamieson A, Muller M, Decker T. 2012. Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection. PLoS Pathog. 8:e1002763. http://dx.doi.org/10.1371/journal.ppat.1002763.
45. Lu B, Ebensperger C, Dembic Z, Wang Y, Kvatyuk M, Lu T, Coffman RL, Pestka S, Rothman PB. 1998. Targeted disruption of the interferongamma receptor 2 gene results in severe immune defects in mice. Proc. Natl. Acad. Sci. U. S. A. 95:8233-8238. http://dx.doi.org/10.1073/pnas.95.14.8233.
46. Auerbuch V, Brockstedt DG, Meyer-Morse N, O'Riordan M, Portnoy DA. 2004. Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J. Exp. Med. 200:527-533. http://dx.doi.org/10.1084/jem.20040976.
47. Carrero JA, Calderon B, Unanue ER. 2004. Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection. J. Exp. Med. 200:535-540. http://dx.doi.org/10.1084/jem.20040769.
48. O'Connell RM, Saha SK, Vaidya SA, Bruhn KW, Miranda GA, Zarnegar B, Perry AK, Nguyen BO, Lane TF, Taniguchi T, Miller JF, Cheng G. 2004. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J. Exp. Med. 200:437-445. http://dx.doi.org/10.1084/jem.20040712.
49. Horvath CM, Stark GR, Kerr IM, Darnell JE, Jr. 1996. Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex. Mol. Cell. Biol. 16:6957-6964.
50. Park C, Lecomte MJ, Schindler C. 1999. Murine Stat2 is uncharacteristically divergent. Nucleic Acids Res. 27:4191-4199. http://dx.doi.org/10.1093/nar/27.21.4191.
51. Paulson M, Pisharody S, Pan L, Guadagno S, Mui AL, Levy DE. 1999. Stat protein transactivation domains recruit p300/CBP through widely divergent sequences. J. Biol. Chem. 274:25343-25349. http://dx.doi.org/10.1074/jbc.274.36.25343.
52. Paulson M, Press C, Smith E, Tanese N, Levy DE. 2002. IFN-stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff. Nat. Cell Biol. 4:140-147. http://dx.doi.org/10.1038/ncb747.
53. Muller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, Zinkernagel RM, Aguet M. 1994. Functional role of type I and type II interferons in antiviral defense. Science 264:1918 -1921. http://dx.doi.org/10.1126/science.8009221.
54. Kundig TM, Hengartner H, Zinkernagel RM. 1993. T cell-dependent IFN-gamma exerts an antiviral effect in the central nervous system but not in peripheral solid organs. J. Immunol. 150:2316-2321.
55. Yoo JY, Huso DL, Nathans D, Desiderio S. 2002. Specific ablation of Stat3beta distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock. Cell 108:331-344. http://dx.doi.org/10.1016/S0092-8674(02)00636-0.
56. Hoey T, Zhang S, Schmidt N, Yu Q, Ramchandani S, Xu X, Naeger LK, Sun YL, Kaplan MH. 2003. Distinct requirements for the naturally occurring splice forms Stat4alpha and Stat4beta in IL-12 responses.EMBOJ. 22:4237-4248. http://dx.doi.org/10.1093/emboj/cdg393.
57. Mo C, Chearwae W, O'Malley JT, Adams SM, Kanakasabai S, Walline CC, Stritesky GL, Good SR, Perumal NB, Kaplan MH, Bright JJ. 2008. Stat4 isoforms differentially regulate inflammation and demyelination in experimental allergic encephalomyelitis. J. Immunol. 181:5681-5690.
58. O'Malley JT, Eri RD, Stritesky GL, Mathur AN, Chang HC, Hogenesch H, Srinivasan M, Kaplan MH. 2008. STAT4 isoforms differentially regulate Th1 cytokine production and the severity of inflammatory bowel disease. J. Immunol. 181:5062-5070.
59. Zhang X, Darnell JE, Jr. 2001. Functional importance of Stat3 tetramerization in activation of the alpha 2-macroglobulin gene. J. Biol. Chem. 276:33576-33581. http://dx.doi.org/10.1074/jbc.M104978200.
60. Zhang X, Wrzeszczynska MH, Horvath CM, Darnell JE, Jr. 1999. Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation. Mol. Cell. Biol. 19:7138-7146.
61. Zhang JJ, Vinkemeier U, Gu W, Chakravarti D, Horvath CM, Darnell JE, Jr. 1996. Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling. Proc. Natl. Acad. Sci. U. S. A. 93:15092-15096. http://dx.doi.org/10.1073/pnas.93.26.15092.
62. Zhu M, John S, Berg M, Leonard WJ. 1999. Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. Cell 96:121-130. http://dx.doi.org/10.1016/S0092-8674(00)80965-4.
63. Kimura T, Kadokawa Y, Harada H, Matsumoto M, Sato M, Kashiwazaki Y, Tarutani M, Tan RS, Takasugi T, Matsuyama T, Mak TW, Noguchi S, Taniguchi T. 1996. Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies. Genes Cells 1:115-124. http://dx.doi.org/10.1046/j.1365-2443.1996.08008.x.
64. Zimmermann A, Trilling M, Wagner M, Wilborn M, Bubic I, Jonjic S, Koszinowski U, Hengel H. 2005. A cytomegaloviral protein reveals a dual role for STAT2 in IFN-{gamma} signaling and antiviral responses. J. Exp. Med. 201:1543-1553. http://dx.doi.org/10.1084/jem.20041401.
65. Bluyssen HA, Muzaffar R, Vlieststra RJ, van der Made AC, Leung S, Stark GR, Kerr IM, Trapman J, Levy DE. 1995. Combinatorial association and abundance of components of interferon-stimulated gene factor 3 dictate the selectivity of interferon responses. Proc. Natl. Acad. Sci. U. S. A. 92:5645-5649. http://dx.doi.org/10.1073/pnas.92.12.5645.
66. Begitt A, Droescher M, Meyer T, Schmid CD, Baker M, Antunes F, Owen MR, Naumann R, Decker T, Vinkemeier U. 2014. STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling. Nat. Immunol. 15:168-176. http://dx.doi.org/10.1038/ni.2794.
67. Morrow AN, Schmeisser H, Tsuno T, Zoon KC. 2011. A novel role for IFN-stimulated gene factor 3II in IFN-gamma signaling and induction of antiviral activity in human cells. J. Immunol. 186:1685-1693. http://dx.doi.org/10.4049/jimmunol.1001359.
68. Ilangumaran S, Rottapel R. 2003. Regulation of cytokine receptor signaling by SOCS1. Immunol. Rev. 192:196-211. http://dx.doi.org/10.1034/j.1600-065X.2003.00020.x.
69. Bullen DV, Darwiche R, Metcalf D, Handman E, Alexander WS. 2001. Neutralization of interferon-gamma in neonatal SOCS1-/- mice prevents fatty degeneration of the liver but not subsequent fatal inflammatory disease. Immunology 104:92-98. http://dx.doi.org/10.1046/j.1365-2567.2001.01294.x.
70. Alexander WS, Starr R, Fenner JE, Scott CL, Handman E, Sprigg NS, Corbin JE, Cornish AL, Darwiche R, Owczarek CM, Kay TW, Nicola NA, Hertzog PJ, Metcalf D, Hilton DJ. 1999. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 98:597-608. http://dx.doi.org/10.1016/S0092-8674(00)80047-1.
71. Miyagi T, Gil MP, Wang X, Louten J, Chu WM, Biron CA. 2007. High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells. J. Exp. Med. 204:2383-2396. http://dx.doi.org/10.1084/jem.20070401.
72. Regis G, Pensa S, Boselli D, Novelli F, Poli V. 2008. Ups and downs: the STAT1:STAT3 seesaw of interferon and gp130 receptor signalling. Semin. Cell Dev. Biol. 19:351-359. http://dx.doi.org/10.1016/j.semcdb.2008.06.004.