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Arthritis Research & Therapy

Erschienen in:

01.08.2004 | Review

Signaling by STATs

verfasst von: Lionel B Ivashkiv, Xiaoyu Hu

Erschienen in: Arthritis Research & Therapy | Ausgabe 4/2004

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Abstract

A variety of cytokines and growth factors use the Janus kinase (Jak)–STAT signaling pathway to transmit extracellular signals to the nucleus. STATs (signal transducers and activators of transcription) are latent cytoplasmic transcription factors. There are seven mammalian STATs and they have critical, nonredundant roles in mediating cellular transcriptional responses to cytokines. The physiological roles of STATs have been elucidated by analysis of mice rendered deficient in STAT genes. STAT activation is regulated and can be modulated in a positive or negative fashion; it can be reprogrammed to drive different cellular responses. Several auto-regulatory and signaling crosstalk mechanisms for regulating Jak–STAT signaling have been described. Understanding and manipulation of the function of STATs will help in the development of therapeutic strategies for diseases that are regulated by cytokines.

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Darnell JE, Kerr IM, Stark GR: Jak–STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994, 264: 1415-1421.CrossRefPubMed

Gauzzi MC, Barbieri G, Richter MF, Uze G, Ling L, Fellous M, Pellegrini S: The amino-terminal region of Tyk2 sustains the level of interferon alpha receptor 1, a component of the interferon alpha/beta receptor. Proc Natl Acad Sci USA. 1997, 94: 11839-11844. 10.1073/pnas.94.22.11839.PubMedCentralCrossRefPubMed

Ivashkiv LB: Cytokines and STATs: how can signals achieve specificity?. Immunity. 1995, 3: 1-4. 10.1016/1074-7613(95)90152-3.CrossRefPubMed

Decker T, Kovarik P: Serine phosphorylation of STATs. Oncogene. 2000, 19: 2628-2637. 10.1038/sj.onc.1203481.CrossRefPubMed

Mowen KA, Tang J, Zhu W, Schurter BT, Shuai K, Herschman HR, David M: Arginine methylation of STAT1 modulates IFNalpha/beta-induced transcription. Cell. 2001, 104: 731-741.CrossRefPubMed

Strobl B, Arulampalam V, Is'harc H, Newman SJ, Schlaak JF, Watling D, Costa-Pereira AP, Schaper F, Behrmann I, Sheehan KC, Schreiber RD, Horn F, Heinrich PC, Kerr IM: A completely foreign receptor can mediate an interferon-gamma-like response. EMBO J. 2001, 20: 5431-5442. 10.1093/emboj/20.19.5431.PubMedCentralCrossRefPubMed

Costa-Pereira AP, Tininini S, Strobl B, Alonzi T, Schlaak JF, Is'harc H, Gesualdo I, Newman SJ, Kerr IM, Poli V: Mutational switch of an IL-6 response to an interferon-gamma-like response. Proc Natl Acad Sci USA. 2002, 99: 8043-8047. 10.1073/pnas.122236099.PubMedCentralCrossRefPubMed

Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T, Akira S: Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA. 1997, 94: 3801-3804. 10.1073/pnas.94.8.3801.PubMedCentralCrossRefPubMed

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: Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK–STAT signaling pathway. Cell. 1996, 84: 431-442. 10.1016/S0092-8674(00)81288-X.CrossRefPubMed

10.

Durbin JE, Hackenmiller R, Simon MC, Levy DE: Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell. 1996, 84: 443-450. 10.1016/S0092-8674(00)81289-1.CrossRefPubMed

11.

Durbin JE, Fernandez-Sesma A, Lee CK, Rao TD, Frey AB, Moran TM, Vukmanovic S, Garcia-Sastre A, Levy DE: Type I IFN modulates innate and specific antiviral immunity. J Immunol. 2000, 164: 4220-4228.CrossRefPubMed

12.

Nishibori T, Tanabe Y, Su L, David M: Impaired development of CD4+ CD25+ regulatory T cells in the absence of STAT1: increased susceptibility to autoimmune disease. J Exp Med. 2004, 199: 25-34. 10.1084/jem.20020509.PubMedCentralCrossRefPubMed

13.

de Hooge A, van de Loo F, Kolbe T, Muller M, Levy D, Bennink M, Arntz O, van den Berg WB: STAT1 and STAT3 activation during the course of experimental arthritis. Arthritis Rheum. 2002, 46: S250-10.1002/1529-0131(200201)46:1<250::AID-ART10064>3.0.CO;2-T.CrossRef

14.

Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD: IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001, 410: 1107-1111. 10.1038/35074122.CrossRefPubMed

15.

Kim S, Koga T, Isobe M, Kern BE, Yokochi T, Chin YE, Karsenty G, Taniguchi T, Takayanagi H: Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. Genes Dev. 2003, 17: 1979-1991. 10.1101/gad.1119303.PubMedCentralCrossRefPubMed

16.

Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, Takaoka A, Yokochi T, Oda H, Tanaka K, Nakamura K, Taniguchi T: T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ. Nature. 2000, 408: 600-605. 10.1038/35046102.CrossRefPubMed

17.

Takayanagi H, Kim S, Matsuo K, Suzuki H, Suzuki T, Sato K, Yokochi T, Oda H, Nakamura K, Ida N, Wagner EF, Taniguchi T: RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β. Nature. 2002, 416: 744-749. 10.1038/416744a.CrossRefPubMed

18.

Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM: IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003, 4: 63-68. 10.1038/ni873.CrossRefPubMed

19.

Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP: IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003, 4: 69-77. 10.1038/ni875.CrossRefPubMed

20.

Park C, Li S, Cha E, Schindler C: Immune response in Stat2 knockout mice. Immunity. 2000, 13: 795-804. 10.1016/S1074-7613(00)00077-7.CrossRefPubMed

21.

Lee CK, Raz R, Gimeno R, Gertner R, Wistinghausen B, Takeshita K, DePinho RA, Levy DE: STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation. Immunity. 2002, 17: 63-72. 10.1016/S1074-7613(02)00336-9.CrossRefPubMed

22.

Welte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE, Bothwell AL, Fikrig E, Koni PA, Flavell RA, Fu XY: STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proc Natl Acad Sci USA. 2003, 100: 1879-1884. 10.1073/pnas.0237137100.PubMedCentralCrossRefPubMed

23.

Takeda K, Kaisho T, Yoshida N, Takeda J, Kishimoto T, Akira S: Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. J Immunol. 1998, 161: 4652-4660.PubMed

24.

Akaishi H, Takeda K, Kaisho T, Shineha R, Satomi S, Takeda J, Akira S: Defective IL-2-mediated IL-2 receptor alpha chain expression in Stat3-deficient T lymphocytes. Int Immunol. 1998, 10: 1747-1751. 10.1093/intimm/10.11.1747.CrossRefPubMed

25.

Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Forster I, Akira S: Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity. 1999, 10: 39-49. 10.1016/S1074-7613(00)80005-9.CrossRefPubMed

26.

Kobayashi M, Kweon MN, Kuwata H, Schreiber RD, Kiyono H, Takeda K, Akira S: Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. J Clin Invest. 2003, 111: 1297-1308. 10.1172/JCI200317085.PubMedCentralCrossRefPubMed

27.

Cheng F, Wang HW, Cuenca A, Huang M, Ghansah T, Brayer J, Kerr WG, Takeda K, Akira S, Schoenberger SP, Yu H, Jove R, Sotomayor EM: A critical role for Stat3 signaling in immune tolerance. Immunity. 2003, 19: 425-436. 10.1016/S1074-7613(03)00232-2.CrossRefPubMed

28.

Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H, Yoshikawa K, Akira S, Takeda J: Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO J. 1999, 18: 4657-4668. 10.1093/emboj/18.17.4657.PubMedCentralCrossRefPubMed

29.

Chapman RS, Lourenco PC, Tonner E, Flint DJ, Selbert S, Takeda K, Akira S, Clarke AR, Watson CJ: Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev. 1999, 13: 2604-2616. 10.1101/gad.13.19.2604.PubMedCentralCrossRefPubMed

30.

Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE: Stat3 as an oncogene. Cell. 1999, 98: 295-303. 10.1016/S0092-8674(00)81959-5.CrossRefPubMed

31.

Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA: Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000, 13: 715-725. 10.1016/S1074-7613(00)00070-4.CrossRefPubMed

32.

Farrar JD, Smith JD, Murphy TL, Leung S, Stark GR, Murphy KM: Selective loss of type I interferon-induced STAT4 activation caused by a minisatellite insertion in mouse Stat2. Nat Immunol. 2000, 1: 65-69. 10.1038/76932.CrossRefPubMed

33.

Kaplan MH, Sun YL, Hoey T, Grusby MJ: Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature. 1996, 382: 174-177. 10.1038/382174a0.CrossRefPubMed

34.

Thierfelder WE, van Deursen JM, Yamamoto K, Tripp RA, Sarawar SR, Carson RT, Sangster MY, Vignali DA, Doherty PC, Grosveld GC, Ihle JN: Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature. 1996, 382: 171-174. 10.1038/382171a0.CrossRefPubMed

35.

Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD: Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003, 421: 744-748. 10.1038/nature01355.CrossRefPubMed

36.

Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN: Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998, 93: 841-850. 10.1016/S0092-8674(00)81444-0.CrossRefPubMed

37.

Nakajima H, Liu XW, Wynshaw-Boris A, Rosenthal LA, Imada K, Finbloom DS, Hennighausen L, Leonard WJ: An indirect effect of Stat5a in IL-2-induced proliferation: a critical role for Stat5a in IL-2-mediated IL-2 receptor alpha chain induction. Immunity. 1997, 7: 691-701. 10.1016/S1074-7613(00)80389-1.CrossRefPubMed

38.

Imada K, Bloom ET, Nakajima H, Horvath-Arcidiacono JA, Udy GB, Davey HW, Leonard WJ: Stat5b is essential for natural killer cell-mediated proliferation and cytolytic activity. J Exp Med. 1998, 188: 2067-2074. 10.1084/jem.188.11.2067.PubMedCentralCrossRefPubMed

39.

Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DA, Doherty PC, Grosveld G, Paul WE, Ihle JN: Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature. 1996, 380: 630-633. 10.1038/380630a0.CrossRefPubMed

40.

Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T, Akira S: Essential role of Stat6 in IL-4 signalling. Nature. 1996, 380: 627-630. 10.1038/380627a0.CrossRefPubMed

41.

Szabo SJ, Dighe AS, Gubler U, Murphy KM: Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med. 1997, 185: 817-824. 10.1084/jem.185.5.817.PubMedCentralCrossRefPubMed

42.

Castro A, Sengupta TK, Ruiz DC, Yang E, Ivashkiv LB: IL-4 selectively inhibits IL-2-triggered Stat5 activation, but not proliferation, in human T cells. J Immunol. 1999, 162: 1261-1269.PubMed

43.

Bach EA, Szabo SJ, Dighe AS, Ashkenazi A, Aguet M, Murphy KM, Schreiber RD: Ligand-induced autoregulation of IFN-gamma receptor beta chain expression in T helper cell subsets. Science. 1995, 270: 1215-1218.CrossRefPubMed

44.

Pernis A, Gupta S, Gollob KJ, Garfein E, Coffman RL, Schindler C, Rothman P: Lack of interferon gamma receptor beta chain and the prevention of interferon gamma signaling in TH1 cells. Science. 1995, 269: 245-247.CrossRefPubMed

45.

Bianchi M, Meng C, Ivashkiv LB: Inhibition of IL-2-induced Jak–STAT signaling by glucocorticoids. Proc Natl Acad Sci USA. 2000, 97: 9573-9578. 10.1073/pnas.160099797.PubMedCentralCrossRefPubMed

46.

Kamura T, Sato S, Haque D, Liu L, Kaelin WG, Conaway RC, Conaway JW: The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families. Genes Dev. 1998, 12: 3872-3881.PubMedCentralCrossRefPubMed

47.

Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, Moritz RL, Cary D, Richardson R, Hausmann G, Kile BJ, Kent SB, Alexander WS, Metcalf D, Hilton DJ, Nicola NA, Baca M: The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Natl Acad Sci USA. 1999, 96: 2071-2076. 10.1073/pnas.96.5.2071.PubMedCentralCrossRefPubMed

48.

Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O: Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1. Mol Cell Biol. 2002, 22: 3316-3326. 10.1128/MCB.22.10.3316-3326.2002.PubMedCentralCrossRefPubMed

49.

Wang D, Moriggl R, Stravopodis D, Carpino N, Marine JC, Teglund S, Feng J, Ihle JN: A small amphipathic alpha-helical region is required for transcriptional activities and proteasome-dependent turnover of the tyrosine-phosphorylated Stat5. EMBO J. 2000, 19: 392-399. 10.1093/emboj/19.3.392.PubMedCentralCrossRefPubMed

50.

Parisien JP, Lau JF, Rodriguez JJ, Sullivan BM, Moscona A, Parks GD, Lamb RA, Horvath CM: The V protein of human parainfluenza virus 2 antagonizes type I interferon responses by destabilizing signal transducer and activator of transcription 2. Virology. 2001, 283: 230-239. 10.1006/viro.2001.0856.CrossRefPubMed

51.

Parisien JP, Lau JF, Rodriguez JJ, Ulane CM, Horvath CM: Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction. J Virol. 2002, 76: 4190-4198. 10.1128/JVI.76.9.4190-4198.2002.PubMedCentralCrossRefPubMed

52.

Ulane CM, Horvath CM: Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes from cellular components. Virology. 2002, 304: 160-166. 10.1006/viro.2002.1773.CrossRefPubMed

53.

Ulane CM, Rodriguez JJ, Parisien JP, Horvath CM: STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling. J Virol. 2003, 77: 6385-6393. 10.1128/JVI.77.11.6385-6393.2003.PubMedCentralCrossRefPubMed

54.

You M, Yu DH, Feng GS: Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway. Mol Cell Biol. 1999, 19: 2416-2424.PubMedCentralCrossRefPubMed

55.

Irie-Sasaki J, Sasaki T, Matsumoto W, Opavsky A, Cheng M, Welstead G, Griffiths E, Krawczyk C, Richardson CD, Aitken K, Iscove N, Koretzky G, Johnson P, Liu P, Rothstein DM, Penninger JM: CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling. Nature. 2001, 409: 349-354. 10.1038/35053086.CrossRefPubMed

56.

Myers MP, Andersen JN, Cheng A, Tremblay ML, Horvath CM, Parisien JP, Salmeen A, Barford D, Tonks NK: TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. J Biol Chem. 2001, 276: 47771-47774. 10.1074/jbc.M009472200.CrossRefPubMed

57.

Haspel RL, Darnell JE: A nuclear protein tyrosine phosphatase is required for the inactivation of Stat1. Proc Natl Acad Sci USA. 1999, 96: 10188-10193. 10.1073/pnas.96.18.10188.PubMedCentralCrossRefPubMed

58.

Wu TR, Hong YK, Wang XD, Ling MY, Dragoi AM, Chung AS, Campbell AG, Han ZY, Feng GS, Chin YE: SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei. J Biol Chem. 2002, 277: 47572-47580. 10.1074/jbc.M207536200.CrossRefPubMed

59.

ten Hoeve J, de Jesus Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, David M, Shuai K: Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol. 2002, 22: 5662-5668. 10.1128/MCB.22.16.5662-5668.2002.PubMedCentralCrossRefPubMed

60.

Yu CL, Jin YJ, Burakoff SJ: Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation. J Biol Chem. 2000, 275: 599-604. 10.1074/jbc.275.1.599.CrossRefPubMed

61.

Liu B, Liao J, Rao X, Kushner SA, Chung CD, Chang DD, Shuai K: Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci USA. 1998, 95: 10626-10631. 10.1073/pnas.95.18.10626.PubMedCentralCrossRefPubMed

62.

Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai K: Specific inhibition of Stat3 signal transduction by PIAS3. Science. 1997, 278: 1803-1805. 10.1126/science.278.5344.1803.CrossRefPubMed

63.

Arora T, Liu B, He H, Kim J, Murphy TL, Murphy KM, Modlin RL, Shuai K: PIASx is a transcriptional co-repressor of signal transducer and activator of transcription 4. J Biol Chem. 2003, 278: 21327-21330. 10.1074/jbc.C300119200.CrossRefPubMed

64.

Liu B, Gross M, ten Hoeve J, Shuai K: A transcriptional co-repressor of Stat1 with an essential LXXLL signature motif. Proc Natl Acad Sci USA. 2001, 98: 3203-3207. 10.1073/pnas.051489598.PubMedCentralCrossRefPubMed

65.

Betz A, Lampen N, Martinek S, Young MW, Darnell JE: A Drosophila PIAS homologue negatively regulates stat92E. Proc Natl Acad Sci USA. 2001, 98: 9563-9568. 10.1073/pnas.171302098.PubMedCentralCrossRefPubMed

66.

Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A: A new protein containing an SH2 domain that inhibits JAK kinases. Nature. 1997, 387: 921-924. 10.1038/43213.CrossRefPubMed

67.

Naka T, Narazaki M, Hirata M, Matsumoto T, Minamoto S, Aono A, Nishimoto N, Kajita T, Taga T, Yoshizaki K, Akira S, Kishimoto T: Structure and function of a new STAT-induced STAT inhibitor. Nature. 1997, 387: 924-929. 10.1038/43219.CrossRefPubMed

68.

Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ: A family of cytokine-inducible inhibitors of signalling. Nature. 1997, 387: 917-921. 10.1038/43206.CrossRefPubMed

69.

Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle J: SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell. 1999, 98: 617-627. 10.1016/S0092-8674(00)80049-5.CrossRefPubMed

70.

Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN: SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell. 1999, 98: 609-616. 10.1016/S0092-8674(00)80048-3.CrossRefPubMed

71.

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: SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell. 1999, 98: 597-608. 10.1016/S0092-8674(00)80047-1.CrossRefPubMed

72.

Nakagawa R, Naka T, Tsutsui H, Fujimoto M, Kimura A, Abe T, Seki E, Sato S, Takeuchi O, Takeda K, Akira S, Yamanishi K, Kawase I, Nakanishi K, Kishimoto T: SOCS-1 participates in negative regulation of LPS responses. Immunity. 2002, 17: 677-687. 10.1016/S1074-7613(02)00449-1.CrossRefPubMed

73.

Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M, Yoshida H, Kubo M, Yoshimura A: SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity. 2002, 17: 583-591. 10.1016/S1074-7613(02)00446-6.CrossRefPubMed

74.

Yasukawa H, Ohishi M, Mori H, Murakami M, Chinen T, Aki D, Hanada T, Takeda K, Akira S, Hoshijima M, Hirano T, Chien KR, Yoshimura A: IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat Immunol. 2003, 4: 551-556. 10.1038/ni938.CrossRefPubMed

75.

Lang R, Pauleau AL, Parganas E, Takahashi Y, Mages J, Ihle JN, Rutschman R, Murray PJ: SOCS3 regulates the plasticity of gp130 signaling. Nat Immunol. 2003, 4: 546-550. 10.1038/ni932.CrossRefPubMed

76.

Croker BA, Krebs DL, Zhang JG, Wormald S, Willson TA, Stanley EG, Robb L, Greenhalgh CJ, Forster I, Clausen BE, Nicola NA, Metcalf D, Hilton DJ, Roberts AW, Alexander WS: SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol. 2003, 4: 540-545. 10.1038/ni931.CrossRefPubMed

77.

Sengupta TK, Schmitt EM, Ivashkiv LB: Inhibition of cytokines and JAK–STAT activation by distinct signaling pathways. Proc Natl Acad Sci USA. 1996, 93: 9499-9504. 10.1073/pnas.93.18.9499.PubMedCentralCrossRefPubMed

78.

Sengupta TK, Talbot ES, Scherle PA, Ivashkiv LB: Rapid inhibition of interleukin-6 signaling and Stat3 activation mediated by mitogen-activated protein kinases. Proc Natl Acad Sci USA. 1998, 95: 11107-11112. 10.1073/pnas.95.19.11107.PubMedCentralCrossRefPubMed

79.

Ahmed ST, Ivashkiv LB: Inhibition of IL-6 and IL-10 signaling and Stat activation by inflammatory and stress pathways. J Immunol. 2000, 165: 5227-5237.CrossRefPubMed

80.

Lee IH, Li WP, Hisert KB, Ivashkiv LB: Inhibition of interleukin 2 signaling and signal transducer and activator of transcription (STAT)5 activation during T cell receptor-mediated feedback inhibition of T cell expansion. J Exp Med. 1999, 190: 1263-1274. 10.1084/jem.190.9.1263.PubMedCentralCrossRefPubMed

81.

Ji JD, Tassiulas I, Park-Min KH, Aydin A, Mecklenbrauker I, Tarakhovsky A, Pricop L, Salmon JE, Ivashkiv LB: Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis. J Exp Med. 2003, 197: 1573-1583. 10.1084/jem.20021820.PubMedCentralCrossRefPubMed

82.

Takaoka A, Mitani Y, Suemori H, Sato M, Yokochi T, Noguchi S, Tanaka N, Taniguchi T: Cross talk between interferon-γ and -α/β signaling components in caveolar membrane domains. Science. 2000, 288: 2357-2360. 10.1126/science.288.5475.2357.CrossRefPubMed

83.

Hu X, Herrero C, Li WP, Antoniv TT, Falck-Pedersen E, Koch AE, Woods JM, Haines GK, Ivashkiv LB: Sensitization of IFN-γ Jak–STAT signaling during macrophage activation. Nat Immunol. 2002, 3: 859-866. 10.1038/ni828.CrossRefPubMed

84.

Malakhova OA, Yan M, Malakhov MP, Yuan Y, Ritchie KJ, Kim KI, Peterson LF, Shuai K, Zhang DE: Protein ISGylation modulates the JAK–STAT signaling pathway. Genes Dev. 2003, 17: 455-460. 10.1101/gad.1056303.PubMedCentralCrossRefPubMed

85.

Sharif MN, Tassiulas I, Hu Y, Mecklenbrauker I, Tarakhovsky A, Ivashkiv LB: IFN-alpha priming results in a gain of proinflammatory function by IL-10: implications for systemic lupus erythematosus pathogenesis. J Immunol. 2004, 172: 6476-6481.CrossRefPubMed

86.

Herrero C, Hu X, Li WP, Samuels S, Sharif MN, Kotenko S, Ivashkiv LB: Reprogramming of IL-10 activity and signaling by IFN-gamma. J Immunol. 2003, 171: 5034-5041.CrossRefPubMed

87.

Ivashkiv LB: Type I interferon modulation of cellular responses to cytokines and infectious pathogens: potential role in SLE pathogenesis. Autoimmunity. 2003, 36: 473-479. 10.1080/08916930310001605882.CrossRefPubMed

88.

Ivashkiv LB, Hu X: The JAK/STAT pathway in rheumatoid arthritis: pathogenic or protective?. Arthritis Rheum. 2003, 48: 2092-2096. 10.1002/art.11095.CrossRefPubMed

89.

van der Pouw Kraan TC, van Gaalen FA, Kasperkovitz PV, Verbeet NL, Smeets TJ, Kraan MC, Fero M, Tak PP, Huizinga TW, Pieterman E, Breedveld FC, Alizadeh AA, Verweij CL: Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues. Arthritis Rheum. 2003, 48: 2132-2145. 10.1002/art.11096.CrossRefPubMed

Titel: Signaling by STATs
verfasst von: Lionel B Ivashkiv
Xiaoyu Hu
Publikationsdatum: 01.08.2004
Verlag: BioMed Central
Erschienen in: Arthritis Research & Therapy / Ausgabe 4/2004
Elektronische ISSN: 1478-6362
DOI: https://doi.org/10.1186/ar1197

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