Important scaffold function of the Janus kinase 2 uncovered by a novel mouse model harboring a Jak2 activation-loop mutation

Blood

Volumn 123, Issue 4, 2014, Pages 520-529

  Keil, Eric ^a   Finkenstädt, David ^a   Wufka, Christian ^a   Trilling, Mirko ^b   Liebfried, Pia ^a   Strobl, Birgit ^c   Müller, Mathias ^c   Pfeffer, Klaus ^a  

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b UNIVERSITY HOSPITAL ESSEN   (Germany)

^c UNIVERSITY OF VETERINARY MEDICINE   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ERYTHROPOIETIN RECEPTOR; GAMMA INTERFERON RECEPTOR 1; JANUS KINASE 1; JANUS KINASE 2; TYROSINE; GAMMA INTERFERON RECEPTOR; INTERFERON RECEPTOR; JAK1 PROTEIN, MOUSE; JAK2 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; EMBRYO; ENZYME ACTIVATION; GENE TARGETING; IN VIVO STUDY; MOUSE; MUTATION; NONHUMAN; NULL ALLELE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; ALLELE; ANIMAL; CELL CULTURE; FIBROBLAST; METABOLISM; PHOSPHORYLATION; TRANSGENIC MOUSE;

ALLELES; ANIMALS; CELLS, CULTURED; FIBROBLASTS; JANUS KINASE 1; JANUS KINASE 2; MICE; MICE, TRANSGENIC; MUTATION; PHENOTYPE; PHOSPHORYLATION; RECEPTORS, ERYTHROPOIETIN; RECEPTORS, INTERFERON; SIGNAL TRANSDUCTION; TYROSINE;

EID: 84897020107     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2013-03-492157     Document Type: Article

References (44)

1. O'Shea JJ, Gadina M, Schreiber RD. Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell. 2002;109(suppl):S121-S131. (Pubitemid 34457857)
2. O'Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immunemediated disease. Immunity. 2012;36(4):542-550.
3. Stark GR, Darnell JE Jr. The JAK-STAT pathway at twenty. Immunity. 2012;36(4):503-514.
4. Chen E, Staudt LM, Green AR. Janus kinase deregulation in leukemia and lymphoma. Immunity. 2012;36(4):529-541.
5. Neubauer H, Cumano A, Müller M, Wu H, Huffstadt U, Pfeffer K. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell. 1998;93(3):397-409. (Pubitemid 28232084)
6. Parganas E, Wang D, Stravopodis D, et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell. 1998;93(3):385-395. (Pubitemid 28232083)
7. Vainchenker W, Dusa A, Constantinescu SN. JAKs in pathology: role of Janus kinases in hematopoietic malignancies and immunodeficiencies. Semin Cell Dev Biol. 2008; 19(4):385-393.
8. Imada K, Leonard WJ. The Jak-STAT pathway. Mol Immunol. 2000;37(1-2):1-11. (Pubitemid 30316189)
9. Baxter EJ, Scott LM, Campbell PJ, et al Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054-1061. (Pubitemid 40386783)
10. James C, Ugo V, Le Couédic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144-1148. (Pubitemid 40663494)
11. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005; 352(17):1779-1790. (Pubitemid 40570926)
12. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387-397. (Pubitemid 40544655)
13. Koppikar P, Bhagwat N, Kilpivaara O, et al. Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy. Nature. 2012;489(7414):155-159.
14. Feng J, Witthuhn BA, Matsuda T, Kohlhuber F, Kerr IM, Ihle JN. Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop. Mol Cell Biol. 1997;17(5): 2497-2501. (Pubitemid 27175130)
15. Chatti K, Farrar WL, Duhé RJ. Tyrosine phosphorylation of the Janus kinase 2 activation loop is essential for a high-activity catalytic state but dispensable for a basal catalytic state. Biochemistry. 2004;43(14):4272- 4283. (Pubitemid 38445648)
16. Bandaranayake RM, Ungureanu D, Shan Y, Shaw DE, Silvennoinen O, Hubbard SR. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F. Nat Struct Mol Biol. 2012;19(8):754-759.
17. O'Sullivan LA, Liongue C, Lewis RS, Stephenson SE, Ward AC. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol. 2007;44(10):2497-2506. (Pubitemid 46240311)
18. Rodig SJ, Meraz MA, White JM, et al. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokineinduced biologic responses. Cell. 1998;93(3): 373-383. (Pubitemid 28232082)
19. LaFave LM, Levine RL. JAK2 the future: therapeutic strategies for JAK-dependent malignancies. Trends Pharmacol Sci. 2012; 33(11):574-582.
20. Andraos R, Qian Z, Bonenfant D, et al. Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent. Cancer Discov. 2012;2(6):512-523.
21. Trilling M, Le VT, Zimmermann A, et al. Gamma interferon-induced interferon regulatory factor 1- dependent antiviral response inhibits vaccinia virus replication in mouse but not human fibroblasts. J Virol. 2009;83(8):3684-3695.
22. Keil E, Hocker R, Schuster M, et al. Phosphorylation of Atg5 by the Gadd45beta- MEKK4-p38 pathway inhibits autophagy. Cell Death Differ. 2013;20(2):321-332.
23. Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994;264(5164):1415-1421. (Pubitemid 24217131)
24. Silvennoinen O, Ihle JN, Schlessinger J, Levy DE. Interferon-induced nuclear signalling by Jak protein tyrosine kinases. Nature. 1993;366(6455): 583-585. (Pubitemid 24036001)
25. Flavell RA, Allen H, Burkly LC, Sherman DH, Waneck GL, Widera G. Molecular biology of the H-2 histocompatibility complex. Science. 1986; 233(4762):437-443. (Pubitemid 16046301)
26. 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(10): 3316-3326. (Pubitemid 34453973)
27. Kohlhuber F, Rogers NC, Watling D, et al. A JAK1/JAK2 chimera can sustain alpha and gamma interferon responses. Mol Cell Biol. 1997; 17(2):695-706. (Pubitemid 27044369)
28. Wen Z, Zhong Z, Darnell JE Jr. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995; 82(2):241-250.
29. Kovarik P, Stoiber D, Eyers PA, et al. Stressinduced phosphorylation of STAT1 at Ser727 requires p38 mitogen-activated protein kinase whereas IFN-gamma uses a different signaling pathway. Proc Natl Acad Sci USA. 1999;96(24): 13956-13961.
30. Varinou L, Ramsauer K, Karaghiosoff M, et al. Phosphorylation of the Stat1 transactivation domain is required for full-fledged IFN-gammadependent innate immunity. Immunity. 2003; 19(6):793-802. (Pubitemid 37542300)
31. Bancerek J, Poss ZC, Steinparzer I, et al. CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity. 2013;38(2):250-262.
32. Kohonen-Corish MR, King NJ, Woodhams CE, Ramshaw IA. Immunodeficient mice recover from infection with vaccinia virus expressing interferongamma. Eur J Immunol. 1990;20(1):157-161. (Pubitemid 20087042)
33. Ahmed CM, Johnson HM. IFN-gamma and its receptor subunit IFNGR1 are recruited to the IFN-gamma-activated sequence element at the promoter site of IFN-gamma-activated genes: evidence of transactivational activity in IFNGR1. J Immunol. 2006;177(1):315-321. (Pubitemid 43939143)
34. Haan C, Kroy DC, Wüller S, et al. An unusual insertion in Jak2 is crucial for kinase activity and differentially affects cytokine responses. J Immunol. 2009;182(5):2969-2977.
35. Frenzel K, Wallace TA, McDoom I, Xiao HD, Capecchi MR, Bernstein KE, Sayeski PP. A functional Jak2 tyrosine kinase domain is essential for mouse development. Exp Cell Res. 2006;312(15):2735-2744.
36. Briscoe J, Rogers NC, Witthuhn BA, et al. Kinasenegative mutants of JAK1 can sustain interferongamma- inducible gene expression but not an antiviral state. EMBO J. 1996;15(4):799-809. (Pubitemid 26064286)
37. Kumar KG, Varghese B, Banerjee A, et al. Basal ubiquitin-independent internalization of interferon alpha receptor is prevented by Tyk2-mediated masking of a linear endocytic motif. J Biol Chem. 2008;283(27):18566-18572.
38. Ragimbeau J, Dondi E, Alcover A, Eid P, Uzé G, Pellegrini S. The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. EMBO J. 2003; 22(3):537-547. (Pubitemid 36193598)
39. Guschin D, Rogers N, Briscoe J, et al. A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 1995;14(7): 1421-1429.
40. Prchal-Murphy M, Semper C, Lassnig C, et al. TYK2 kinase activity is required for functional type I interferon responses in vivo. PLoS ONE. 2012; 7(6):e39141.
41. Li Z, Gakovic M, Ragimbeau J, et al. Two rare disease-associated Tyk2 variants are catalytically impaired but signaling competent. J Immunol. 2013;190(5):2335-2344.
42. Strobl B, Stoiber D, Sexl V, Mueller M. Tyrosine kinase 2 (TYK2) in cytokine signalling and host immunity. Front Biosci (Landmark Ed). 2011;16: 3214-3232.
43. Zhou YJ, Hanson EP, Chen YQ, et al. Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity. Proc Natl Acad Sci USA. 1997; 94(25):13850-13855. (Pubitemid 28009673)
44. Liu KD, Gaffen SL, Goldsmith MA, Greene WC. Janus kinases in interleukin-2-mediated signaling: JAK1 and JAK3 are differentially regulated by tyrosine phosphorylation. Curr Biol. 1997;7(11): 817-826. (Pubitemid 27493120)