Tyk2

Summary

Gene Symbol: Tyk2
Description: tyrosine kinase 2
Alias: JTK1, non-receptor tyrosine-protein kinase TYK2, tyrosine kinase TYK2
Species: mouse
Products:     Tyk2

Top Publications

  1. Shimoda K, Tsutsui H, Aoki K, Kato K, Matsuda T, Numata A, et al. Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice. Blood. 2002;99:2094-9 pubmed
    b>Tyk2 is activated in response to interleukin-12 (IL-12) and is essential for IL-12-induced T-cell function, including interferon-gamma (IFN-gamma) production and Th1 cell differentiation...
  2. Shimoda K, Kamesaki K, Numata A, Aoki K, Matsuda T, Oritani K, et al. Cutting edge: tyk2 is required for the induction and nuclear translocation of Daxx which regulates IFN-alpha-induced suppression of B lymphocyte formation. J Immunol. 2002;169:4707-11 pubmed
    ..inhibits the clonal proliferation of B lymphocyte progenitors in response to IL-7 in wild-type, but not in tyk2-deficient, mice...
  3. Potla R, Koeck T, Wegrzyn J, Cherukuri S, Shimoda K, Baker D, et al. Tyk2 tyrosine kinase expression is required for the maintenance of mitochondrial respiration in primary pro-B lymphocytes. Mol Cell Biol. 2006;26:8562-71 pubmed
    b>Tyk2, a member of the Jak family of protein tyrosine kinases, is critical for the biological actions of alpha/beta interferon (IFN-alpha/beta)...
  4. Shaw M, Boyartchuk V, Wong S, Karaghiosoff M, Ragimbeau J, Pellegrini S, et al. A natural mutation in the Tyk2 pseudokinase domain underlies altered susceptibility of B10.Q/J mice to infection and autoimmunity. Proc Natl Acad Sci U S A. 2003;100:11594-9 pubmed
    ..Using genetic approaches, we have now localized the B10.Q/J locus to chromosome 9 and established its identity as Tyk2, a Janus kinase essential for IL-12 and IFN-alpha/beta cytokine signaling. The B10...
  5. Karaghiosoff M, Steinborn R, Kovarik P, Kriegshäuser G, Baccarini M, Donabauer B, et al. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat Immunol. 2003;4:471-7 pubmed
    ..Here we report that mice devoid of the JAK protein tyrosine kinase family member, Tyk2, were resistant to shock induced by high doses of LPS...
  6. Seto Y, Nakajima H, Suto A, Shimoda K, Saito Y, Nakayama K, et al. Enhanced Th2 cell-mediated allergic inflammation in Tyk2-deficient mice. J Immunol. 2003;170:1077-83 pubmed
    ..b>Tyk2 is a member of the Janus family of protein tyrosine kinases and is activated by a variety of cytokines: IFN-..
  7. Strobl B, Bubic I, Bruns U, Steinborn R, Lajko R, Kolbe T, et al. Novel functions of tyrosine kinase 2 in the antiviral defense against murine cytomegalovirus. J Immunol. 2005;175:4000-8 pubmed
    We have recently reported that tyrosine kinase 2 (Tyk2)-deficient mice have a selective defect in the in vivo defense against certain viruses. In our current study we show that Tyk2 is essential for the defense against murine CMV (MCMV)...
  8. Shimoda K, Kato K, Aoki K, Matsuda T, Miyamoto A, Shibamori M, et al. Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function. Immunity. 2000;13:561-71 pubmed
    Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo...
  9. Karaghiosoff M, Neubauer H, Lassnig C, Kovarik P, Schindler H, Pircher H, et al. Partial impairment of cytokine responses in Tyk2-deficient mice. Immunity. 2000;13:549-60 pubmed
    To assess the role of the Janus kinase (Jak) family member Tyk2, we have generated Tyk2-/- mice...

More Information

Publications72

  1. Piganis R, de Weerd N, Gould J, Schindler C, Mansell A, Nicholson S, et al. Suppressor of cytokine signaling (SOCS) 1 inhibits type I interferon (IFN) signaling via the interferon alpha receptor (IFNAR1)-associated tyrosine kinase Tyk2. J Biol Chem. 2011;286:33811-8 pubmed publisher
    ..with the IFN ? receptor 1 (IFNAR1) receptor component but through an interaction with the IFNAR1-associated kinase Tyk2. We have characterized the residues/regions involved in the interaction between SOCS1 and Tyk2 and found that SOCS1 ..
  2. Blanc M, Hsieh W, Robertson K, Watterson S, Shui G, Lacaze P, et al. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol. 2011;9:e1000598 pubmed publisher
    ..knockout of the receptor for all type I interferon family members, ifnar1, or associated signaling component, tyk2, completely abolishes the reduction of the sterol biosynthetic activity upon infection...
  3. Ragimbeau J, Dondi E, Alcover A, Eid P, Uze G, Pellegrini S. The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. EMBO J. 2003;22:537-47 pubmed
    ..In the type I interferon receptor, Tyk2 associates with the IFNAR1 receptor subunit and positively influences ligand binding to the receptor complex...
  4. Vogl C, Flatt T, Fuhrmann B, Hofmann E, Wallner B, Stiefvater R, et al. Transcriptome analysis reveals a major impact of JAK protein tyrosine kinase 2 (Tyk2) on the expression of interferon-responsive and metabolic genes. BMC Genomics. 2010;11:199 pubmed publisher
    Tyrosine kinase 2 (Tyk2), a central component of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, has major effects on innate immunity and inflammation...
  5. Kamezaki K, Shimoda K, Numata A, Matsuda T, Nakayama K, Harada M. The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals. Int Immunol. 2004;16:1173-9 pubmed
    Mice lacking Tyk2, Stat1 or Stat4, which are members of the Jak-Stat signaling cascade, were resistant to LPS-induced endotoxin shock...
  6. Oyamada A, Ikebe H, Itsumi M, Saiwai H, Okada S, Shimoda K, et al. Tyrosine kinase 2 plays critical roles in the pathogenic CD4 T cell responses for the development of experimental autoimmune encephalomyelitis. J Immunol. 2009;183:7539-46 pubmed publisher
    Tyrosine kinase 2 (Tyk2), a member of the JAK family, is involved in IL-12- and IL-23-mediated signaling...
  7. Spach K, Noubade R, McElvany B, Hickey W, Blankenhorn E, Teuscher C. A single nucleotide polymorphism in Tyk2 controls susceptibility to experimental allergic encephalomyelitis. J Immunol. 2009;182:7776-83 pubmed publisher
    ..B10.D1-H2(q)/SgJ mice with a 2538 G-->A missense mutation in the tyrosine kinase-2 gene (Tyk2) are susceptible to Toxoplasma gondii yet resistant to autoimmune arthritis, unlike the wild-type B10...
  8. Wesley J, Tessmer M, Paget C, Trottein F, Brossay L. A Y chromosome-linked factor impairs NK T development. J Immunol. 2007;179:3480-7 pubmed
    ..Analysis of the Valpha14i NK T cell compartment in B6.Tyk2-/-, B6.STAT1-/-, 129.IFN-alphabetaR1-/-, and B6...
  9. Aoki K, Shimoda K, Oritani K, Matsuda T, Kamezaki K, Muromoto R, et al. Limitin, an interferon-like cytokine, transduces inhibitory signals on B-cell growth through activation of Tyk2, but not Stat1, followed by induction and nuclear translocation of Daxx. Exp Hematol. 2003;31:1317-22 pubmed
    ..81, wild-type, and Tyk2-deficient mouse bone marrow cells...
  10. Ishizaki M, Akimoto T, Muromoto R, Yokoyama M, Ohshiro Y, Sekine Y, et al. Involvement of tyrosine kinase-2 in both the IL-12/Th1 and IL-23/Th17 axes in vivo. J Immunol. 2011;187:181-9 pubmed publisher
    Tyrosine kinase-2 (Tyk2), a member of the Jak family of kinases, mediates the signals triggered by various cytokines, including type I IFNs, IL-12, and IL-23...
  11. Radwan M, Stiefvater R, Grunert T, Sharif O, Miller I, Marchetti Deschmann M, et al. Tyrosine kinase 2 controls IL-1ß production at the translational level. J Immunol. 2010;185:3544-53 pubmed publisher
    ..levels in macrophages derived from murine bone marrow are markedly increased in the absence of tyrosine kinase 2 (Tyk2). Increased IL-1beta is found intra- and extracellularly, irrespective of the efficiency of IL-1beta processing...
  12. Schleicher U, Mattner J, Blos M, Schindler H, Rollinghoff M, Karaghiosoff M, et al. Control of Leishmania major in the absence of Tyk2 kinase. Eur J Immunol. 2004;34:519-29 pubmed
    ..Here, we investigated in the Leishmania major mouse model whether Tyk2 kinase is required for the generation of a protective immune response...
  13. Zou J, Presky D, Wu C, Gubler U. Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits beta1 and beta2 and JAK kinases. J Biol Chem. 1997;272:6073-7 pubmed
    ..EGF-dependent phosphorylation of E12R2, JAK2, Tyk2, and STAT3 was observed. JAK2 was phosphorylated in E12R1-, E12R2-, and E12R1+E12R2-expressing cells...
  14. Stoiber D, Kovacic B, Schuster C, Schellack C, Karaghiosoff M, Kreibich R, et al. TYK2 is a key regulator of the surveillance of B lymphoid tumors. J Clin Invest. 2004;114:1650-8 pubmed
    ..We show here that the Janus kinase TYK2 serves an opposite function...
  15. Grunert T, Leitner N, Marchetti Deschmann M, Miller I, Wallner B, Radwan M, et al. A comparative proteome analysis links tyrosine kinase 2 (Tyk2) to the regulation of cellular glucose and lipid metabolism in response to poly(I:C). J Proteomics. 2011;74:2866-80 pubmed publisher
    Tyrosine kinase 2 (Tyk2) is an integral part of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway which relays intracellular signals of various cytokines...
  16. Ortmann R, Smeltz R, Yap G, Sher A, Shevach E. A heritable defect in IL-12 signaling in B10.Q/J mice. I. In vitro analysis. J Immunol. 2001;166:5712-9 pubmed
    ..This subtle abnormality in IL-12 responsiveness results in a profound defect in the generation of Th1 cells and the development of autoimmune disease. ..
  17. Zeng B, Li H, Liu Y, Zhang Z, Zhang Y, Yang R. Tumor-induced suppressor of cytokine signaling 3 inhibits toll-like receptor 3 signaling in dendritic cells via binding to tyrosine kinase 2. Cancer Res. 2008;68:5397-404 pubmed publisher
    ..Immunoprecipitation and pull-down studies show that SOCS3 binds to the IFNalpha receptor tyrosine kinase 2 (TYK2)...
  18. Simma O, Zebedin E, Neugebauer N, Schellack C, Pilz A, Chang Rodriguez S, et al. Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance. Cancer Res. 2009;69:203-11 pubmed publisher
    We showed previously that Tyk2(-/-) natural killer cells lack the ability to lyse leukemic cells. As a consequence, the animals are leukemia prone. Here, we show that the impaired tumor surveillance extends to T cells...
  19. Tokumasa N, Suto A, Kagami S, Furuta S, Hirose K, Watanabe N, et al. Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-gamma production and the induction of Th1 cell differentiation. Blood. 2007;110:553-60 pubmed
    ..In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions...
  20. Sugimoto N, Nakahira M, Ahn H, Micallef M, Hamaoka T, Kurimoto M, et al. Differential requirements for JAK2 and TYK2 in T cell proliferation and IFN-gamma production induced by IL-12 alone or together with IL-18. Eur J Immunol. 2003;33:243-51 pubmed
    IL-12 activates TYK2 and Janus kinase (JAK)-2 to induce the phosphorylation of various signal transducers and activators of transcription (STAT) proteins...
  21. Yap G, Ortmann R, Shevach E, Sher A. A heritable defect in IL-12 signaling in B10.Q/J mice. II. Effect on acute resistance to Toxoplasma gondii and rescue by IL-18 treatment. J Immunol. 2001;166:5720-5 pubmed
    ..Q/J mice can result in defective host resistance and demonstrate a therapeutic function for IL-18 in reversing a genetically based immunodeficiency in IL-12-dependent IFN-gamma production. ..
  22. Dendrou C, Cortes A, Shipman L, Evans H, Attfield K, Jostins L, et al. Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med. 2016;8:363ra149 pubmed
    ..Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 ..
  23. Ishizaki M, Muromoto R, Akimoto T, Sekine Y, Kon S, Diwan M, et al. Tyk2 is a therapeutic target for psoriasis-like skin inflammation. Int Immunol. 2014;26:257-67 pubmed publisher
    Tyrosine kinase 2 (Tyk2), a member of the Jak kinase family, mediates signals triggered by various cytokines, which are related to the pathogenesis of psoriasis...
  24. Gamero A, Potla R, Wegrzyn J, Szelag M, Edling A, Shimoda K, et al. Activation of Tyk2 and Stat3 is required for the apoptotic actions of interferon-beta in primary pro-B cells. J Biol Chem. 2006;281:16238-44 pubmed
    ..However, in pro-B cells from Tyk2(-/-) mice, where there is normal activation of Stat1 and Stat2, IFNbeta-stimulated PCD is not observed...
  25. Gingras S, Parganas E, de Pauw A, Ihle J, Murray P. Re-examination of the role of suppressor of cytokine signaling 1 (SOCS1) in the regulation of toll-like receptor signaling. J Biol Chem. 2004;279:54702-7 pubmed
    ..Furthermore, the absence of a single allele encoding TYK2, a JAK (Janus kinase) family member essential IFN-alpha/beta receptor signaling, rescued Socs1-/- mice from early ..
  26. Argiriadi M, Goedken E, Banach D, Borhani D, Burchat A, Dixon R, et al. Enabling structure-based drug design of Tyk2 through co-crystallization with a stabilizing aminoindazole inhibitor. BMC Struct Biol. 2012;12:22 pubmed publisher
    ..Here we present the first mouse Tyk2 crystal structures, which are complexed to 3-aminoindazole compounds...
  27. Vielnascher R, Hainzl E, Leitner N, Rammerstorfer M, Popp D, Witalisz A, et al. Conditional ablation of TYK2 in immunity to viral infection and tumor surveillance. Transgenic Res. 2014;23:519-29 pubmed publisher
    Tyrosine kinase 2 (TYK2) has a pivotal role in immunity to infection and tumor surveillance...
  28. Deb C, Lafrance Corey R, Zoecklein L, Papke L, Rodriguez M, Howe C. Demyelinated axons and motor function are protected by genetic deletion of perforin in a mouse model of multiple sclerosis. J Neuropathol Exp Neurol. 2009;68:1037-48 pubmed publisher
    ..These results suggest that perforin is a key mediator of axon injury and lend additional support to the hypothesis that CD8 T cells are primarily responsible for axon damage in multiple sclerosis. ..
  29. Ruiz J, Conlon F, Robertson E. Identification of novel protein kinases expressed in the myocardium of the developing mouse heart. Mech Dev. 1994;48:153-64 pubmed
    ..75-8.5 dpc developing heart. Subsequently, msk mRNA expression is rapidly downregulated. The patterns of Hek2 and msk expression suggest that these protein kinases may function during development of the primitive heart. ..
  30. Linossi E, Chandrashekaran I, Kolesnik T, Murphy J, Webb A, Willson T, et al. Suppressor of Cytokine Signaling (SOCS) 5 utilises distinct domains for regulation of JAK1 and interaction with the adaptor protein Shc-1. PLoS ONE. 2013;8:e70536 pubmed publisher
    ..Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2) autophosphorylation and this function required both the conserved JIR and additional sequences within the long ..
  31. Übel C, Graser A, Koch S, Rieker R, Lehr H, Müller M, et al. Role of Tyk-2 in Th9 and Th17 cells in allergic asthma. Sci Rep. 2014;4:5865 pubmed publisher
    ..These results suggest a role of Tyk-2 in different subsets of T helper cells mediated by SOCS3 regulation that is relevant for the treatment of asthma, cancer and autoimmune diseases. ..
  32. Yamaji T, Shide K, Kameda T, Sekine M, Kamiunten A, Hidaka T, et al. Loss of Tyrosine Kinase 2 Does Not Affect the Severity of Jak2V617F-induced Murine Myeloproliferative Neoplasm. Anticancer Res. 2017;37:3841-3847 pubmed
    ..It is unclear whether JAK kinases [i.e. JAK1, JAK2, JAK3, or tyrosine kinase 2 (TYK2)] other than JAK2 have cooperative actions such as enhancement or suppression of JAK2...
  33. Prchal Murphy M, Semper C, Lassnig C, Wallner B, Gausterer C, Teppner Klymiuk I, et al. TYK2 kinase activity is required for functional type I interferon responses in vivo. PLoS ONE. 2012;7:e39141 pubmed publisher
    Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in cytokine signalling. In vitro analyses suggest that TYK2 also has kinase-independent, i.e., non-canonical, functions...
  34. Raje V, Derecka M, Cantwell M, Meier J, Szczepanek K, Sisler J, et al. Kinase Inactive Tyrosine Kinase (Tyk2) Supports Differentiation of Brown Fat Cells. Endocrinology. 2017;158:148-157 pubmed publisher
    ..We have recently identified that in addition to PRDM16, the tyrosine kinase Tyk2 and the STAT3 transcription factor are required for the differentiation of Myf5 positive brown ..
  35. Schuster C, Muller M, Freissmuth M, Sexl V, Stoiber D. Commentary on H. Ide et al., "Tyk2 expression and its signaling enhances the invasiveness of prostate cancer cells". Biochem Biophys Res Commun. 2008;366:869-70 pubmed
  36. Li J. JAK-STAT and bone metabolism. JAKSTAT. 2013;2:e23930 pubmed publisher
    ..Selective inactivation of STAT3 in osteoblasts decreases bone formation and skeletal responsiveness to mechanical loading. Future research includes investigating JAK-STAT signaling in osteoclasts and osteocytes. ..
  37. Smith C, Arvedson T, Cooke K, Dickmann L, Forte C, Li H, et al. IL-22 regulates iron availability in vivo through the induction of hepcidin. J Immunol. 2013;191:1845-55 pubmed publisher
    ..This response was independent of IL-6 and was attenuated in the absence of the IL-22R-associated signaling kinase, Tyk2. Ab-mediated blockade of hepcidin partially reversed the effects on iron biology caused by IL-22R stimulation...
  38. Peng D, Zeng M, Muromoto R, Matsuda T, Shimoda K, Subramaniam M, et al. Noncanonical K27-linked polyubiquitination of TIEG1 regulates Foxp3 expression and tumor growth. J Immunol. 2011;186:5638-47 pubmed publisher
    ..b>Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which ..
  39. Bieber A, Suwansrinon K, Kerkvliet J, Zhang W, Pease L, Rodriguez M. Allelic variation in the Tyk2 and EGF genes as potential genetic determinants of CNS repair. Proc Natl Acad Sci U S A. 2010;107:792-7 pubmed publisher
    ..3 and a second on chromosome 9 with a LOD score of 14.0. The mouse genes for epidermal growth factor (EGF) and Tyk2 are encoded within the QTL on chromosomes 3 and 9, respectively. Sequence polymorphisms between the FVB and B10...
  40. Hashiguchi T, Oyamada A, Sakuraba K, Shimoda K, Nakayama K, Iwamoto Y, et al. Tyk2-dependent bystander activation of conventional and nonconventional Th1 cell subsets contributes to innate host defense against Listeria monocytogenes infection. J Immunol. 2014;192:4739-47 pubmed publisher
    ..the development and the functions of the different subsets of Th1 cells by using mice lacking tyrosine kinase 2 (Tyk2), a member of the Janus kinase family critically involved in IL-12 signaling...
  41. Schneider A, Reichart U, Gerner W, Kolbe T, Saalmuller A, Muller M. Selective contribution of Tyk2 to cell activation by lipopolysaccharide. FEBS Lett. 2008;582:3681-6 pubmed publisher
    b>Tyk2 deficient mice show a markedly reduced susceptibility to lipopolysaccharide (LPS) induced shock and a partial impairment of IL-12 and interferon (IFN) signals...
  42. Works M, Yin F, Yin C, Yiu Y, Shew K, Tran T, et al. Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. J Immunol. 2014;193:3278-87 pubmed publisher
    ..we report the activity of SAR-20347, a small molecule inhibitor with specificity for JAK1 and tyrosine kinase 2 (TYK2) over other JAK family members...
  43. Li W, Yamada H, Yajima T, Nakagawa R, Shimoda K, Nakayama K, et al. Tyk2 signaling in host environment plays an important role in contraction of antigen-specific CD8+ T cells following a microbial infection. J Immunol. 2007;178:4482-8 pubmed
    Tyrosine kinase 2 (Tyk2), a member of JAK signal transducer family contributes to the signals triggered by IL-12 for IFN-gamma production...
  44. Bosmann M, Strobl B, Kichler N, Rigler D, Grailer J, Pache F, et al. Tyrosine kinase 2 promotes sepsis-associated lethality by facilitating production of interleukin-27. J Leukoc Biol. 2014;96:123-31 pubmed publisher
    The aim of this study was to test the hypothesis that gene expression and release of IL-27 may be modulated by Tyk2. Macrophages derived from the peritoneum or bone marrow of C57BL/10SnJ (WT) mice produced abundant amounts of IL-27(p28) ..
  45. Wilbers R, van Raaij D, Westerhof L, Bakker J, Smant G, Schots A. Re-evaluation of IL-10 signaling reveals novel insights on the contribution of the intracellular domain of the IL-10R2 chain. PLoS ONE. 2017;12:e0186317 pubmed publisher
    ..Engagement of the IL-10R complex activates the intracellular kinases Jak1 and Tyk2, but the exact roles of IL-10R2 and IL-10R2-associated signaling via Tyk2 remain unclear...
  46. Zhang Q, Sturgill J, Kmieciak M, Szczepanek K, Derecka M, Koebel C, et al. The role of Tyk2 in regulation of breast cancer growth. J Interferon Cytokine Res. 2011;31:671-7 pubmed publisher
    ..and Jak2, resulting in activation of the Stat1 transcription factor, whereas type 1 IFNs (IFN?/?) activate Jak1 and Tyk2, which mediate their effects through Stat1 and Stat2...
  47. Wilson D, Matthews S, Yap G. IL-12 signaling drives CD8+ T cell IFN-gamma production and differentiation of KLRG1+ effector subpopulations during Toxoplasma gondii Infection. J Immunol. 2008;180:5935-45 pubmed
    ..gondii...
  48. Derecka M, Gornicka A, Koralov S, Szczepanek K, Morgan M, Raje V, et al. Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity. Cell Metab. 2012;16:814-24 pubmed publisher
    Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT)...
  49. Kanagasundaram V, Jaworowski A, Byrne R, Hamilton J. Separation and characterization of the activated pool of colony-stimulating factor 1 receptor forming distinct multimeric complexes with signalling molecules in macrophages. Mol Cell Biol. 1999;19:4079-92 pubmed
    ..Specific structural proteins associated with the separate CSF-1R multimeric complexes upon CSF-1 stimulation and the presence of the distinct pools of the CSF-1R were dependent on the integrity of the microtubular network. ..
  50. Aizu K, Li W, Yajima T, Arai T, Shimoda K, Nimura Y, et al. An important role of Tyk2 in APC function of dendritic cells for priming CD8+ T cells producing IFN-gamma. Eur J Immunol. 2006;36:3060-70 pubmed
    Tyrosine kinase 2 (Tyk2) contributes to the signals triggered by IL-12 for IFN-gamma production by NK cells and T cells. We found in this study that Tyk2-deficient (-/-) mice showed increased susceptibility at the early stage after an i.p...
  51. Shaw M, Freeman G, Scott M, Fox B, Bzik D, Belkaid Y, et al. Tyk2 negatively regulates adaptive Th1 immunity by mediating IL-10 signaling and promoting IFN-gamma-dependent IL-10 reactivation. J Immunol. 2006;176:7263-71 pubmed
    The Jak, Tyk2, is activated in response to IL-12 and IFN-alphabeta and promotes IFN-gamma production by Th1-type CD4 cells...
  52. Mostafavi S, Yoshida H, Moodley D, LeBoité H, Rothamel K, Raj T, et al. Parsing the Interferon Transcriptional Network and Its Disease Associations. Cell. 2016;164:564-78 pubmed publisher
  53. Babon J, Lucet I, Murphy J, Nicola N, Varghese L. The molecular regulation of Janus kinase (JAK) activation. Biochem J. 2014;462:1-13 pubmed publisher
    ..This family, comprising JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), was first described more than 20 years ago, but the complexities underlying their activation, ..
  54. Nakamura R, Shibata K, Yamada H, Shimoda K, Nakayama K, Yoshikai Y. Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by gammadelta T cells. J Immunol. 2008;181:2071-5 pubmed
    Tyrosine kinase 2 (Tyk2), a member of the JAK-signal transducer family, is involved in intracellular signaling triggered by various cytokines, including IL-23...
  55. Painz R, Walter I, Kolbe T, Rigler D, Vogl C, Steinborn R, et al. Organ-specific and differential requirement of TYK2 and IFNAR1 for LPS-induced iNOS expression in vivo. Immunobiology. 2007;212:863-75 pubmed
    ..The Janus kinase (JAK) family member tyrosine kinase 2 (TYK2) is a constituent of the interferon (IFN) type I response pathway and an important effector in the progression of ..
  56. Senft A, Taylor R, Lei W, Campbell S, Tipper J, Martinez M, et al. Respiratory syncytial virus impairs macrophage IFN-alpha/beta- and IFN-gamma-stimulated transcription by distinct mechanisms. Am J Respir Cell Mol Biol. 2010;42:404-14 pubmed publisher
  57. Brunskill E, Witte D, Yutzey K, Potter S. Novel cell lines promote the discovery of genes involved in early heart development. Dev Biol. 2001;235:507-20 pubmed
    ..The results show that the 1H and ECL-2 cell lines can be used to discover novel genes expressed in the early cardiomyocyte. ..
  58. Ishizaki M, Muromoto R, Akimoto T, Ohshiro Y, Takahashi M, Sekine Y, et al. Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice. Int Immunol. 2011;23:575-82 pubmed publisher
    Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity...
  59. Alazawi W, Heath H, Waters J, Woodfin A, O Brien A, Scarzello A, et al. Stat2 loss leads to cytokine-independent, cell-mediated lethality in LPS-induced sepsis. Proc Natl Acad Sci U S A. 2013;110:8656-61 pubmed publisher
    ..Thus, our data reveal the existence of a different mechanism of LPS-induced lethality that is independent of NF-?B triggered cytokine storm but dependent on cellular egress. ..
  60. Izumi K, Mine K, Inoue Y, Teshima M, Ogawa S, Kai Y, et al. Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes. Nat Commun. 2015;6:6748 pubmed publisher
    ..We report here that novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced diabetes-sensitive SJL and SWR mice...
  61. Hainzl E, Stockinger S, Rauch I, Heider S, Berry D, Lassnig C, et al. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis. J Immunol. 2015;195:5011-24 pubmed publisher
    ..The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family...
  62. Hosogi M, Tonogaito H, Aioi A, Hamada K, Shimoda K, Muromoto R, et al. Hapten-induced contact hypersensitivity is enhanced in Tyk2-deficient mice. J Dermatol Sci. 2004;36:51-6 pubmed
    Previous studies have shown that Tyk2, a member of the Janus family of protein tyrosine kinases, which are activated by a variety of cytokines, plays a crucial role in interleukin (IL)-12-mediated T-cell functions such as IFN-gamma ..
  63. Chung B, Kang H, Han S, Heo H, Lee J, Jeon J, et al. Jak2 and Tyk2 are necessary for lineage-specific differentiation, but not for the maintenance of self-renewal of mouse embryonic stem cells. Biochem Biophys Res Commun. 2006;351:682-8 pubmed
    ..By employing an RNAi strategy, we established both Jak2 and Jak2/Tyk2 knockdown mESC clones...