Tyk2

Summary

Gene Symbol: Tyk2
Description: tyrosine kinase 2
Alias: IMD35, JTK1, non-receptor tyrosine-protein kinase TYK2
Species: human
Products:     Tyk2

Top Publications

  1. Velazquez L, Fellous M, Stark G, Pellegrini S. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. 1992;70:313-22 pubmed
    ..Complementary DNAs were cloned and found to be virtually identical to tyk2, a human mRNA encoding a non-receptor protein tyrosine kinase of previously unknown function...
  2. Firmbach Kraft I, Byers M, Shows T, Dalla Favera R, Krolewski J. tyk2, prototype of a novel class of non-receptor tyrosine kinase genes. Oncogene. 1990;5:1329-36 pubmed
    We previously identified a novel protein tyrosine kinase gene, tyk2, by screening a human lymphoid cDNA library with a tyrosine kinase domain specific c-fms restriction fragment under low stringency hybridization conditions...
  3. Colamonici O, Yan H, Domanski P, Handa R, Smalley D, Mullersman J, et al. Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase. Mol Cell Biol. 1994;14:8133-42 pubmed
    ..The association between the alpha subunit and Tyk2 was demonstrated by immunoblotting with anti-Tyk2 and antiphosphotyrosine antibodies and by using an in vitro ..
  4. Gauzzi M, Barbieri G, Richter M, Uze G, Ling L, Fellous M, et al. 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 U S A. 1997;94:11839-44 pubmed
    b>Tyk2 belongs to the Janus kinase (JAK) family of receptor associated tyrosine kinases, characterized by a large N-terminal region, a kinase-like domain and a tyrosine kinase domain...
  5. Ban M, Goris A, Lorentzen A, Baker A, Mihalova T, Ingram G, et al. Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. Eur J Hum Genet. 2009;17:1309-13 pubmed publisher
    ..evidence for association was substantially increased for one of the 17 loci, rs34536443 from the tyrosine kinase 2 (TYK2) gene (P=2.7 x 10(-6), odds ratio=1.32 (1.17-1.47))...
  6. Wallace C, Smyth D, Maisuria Armer M, Walker N, Todd J, Clayton D. The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. Nat Genet. 2010;42:68-71 pubmed publisher
    ..2. The highest association was at marker rs2304256 (odds ratio (OR) = 0.86; 95%CI = 0.82-0.90) in the TYK2 gene, which has previously been associated with systemic lupus erythematosus and multiple sclerosis.
  7. Sanda T, Tyner J, Gutierrez A, Ngo V, Glover J, Chang B, et al. TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia. Cancer Discov. 2013;3:564-77 pubmed publisher
    ..screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effector STAT1, in T-cell acute lymphoblastic leukemia (T-ALL)...
  8. Richter M, Dumenil G, Uze G, Fellous M, Pellegrini S. Specific contribution of Tyk2 JH regions to the binding and the expression of the interferon alpha/beta receptor component IFNAR1. J Biol Chem. 1998;273:24723-9 pubmed
    ..Here, we sought to define the molecular basis of the interaction between Tyk2 and IFNAR1, a component of the interferon alpha/beta receptor, by delimiting a minimal IFNAR1 binding region in the ..
  9. Rani M, Leaman D, Han Y, Leung S, Croze E, Fish E, et al. Catalytically active TYK2 is essential for interferon-beta-mediated phosphorylation of STAT3 and interferon-alpha receptor-1 (IFNAR-1) but not for activation of phosphoinositol 3-kinase. J Biol Chem. 1999;274:32507-11 pubmed
    b>TYK2, a Janus kinase, plays both structural and catalytic roles in type I interferon (IFN) signaling. We recently reported (Rani, M. R. S., Gauzzi, C., Pellegrini, S., Fish, E., Wei, T., and Ransohoff, R. M. (1999) J. Biol. Chem...

More Information

Publications114 found, 100 shown here

  1. 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...
  2. Cunninghame Graham D, Akil M, Vyse T. Association of polymorphisms across the tyrosine kinase gene, TYK2 in UK SLE families. Rheumatology (Oxford). 2007;46:927-30 pubmed
    This is a family-based association study to investigate the genetic contribution of tyrosine kinase 2 (TYK2 ) to disease susceptibility in 380 UK systemic lupus erythematosus (SLE) families, consisting of parents and affected offspring...
  3. Kumar K, Varghese B, Banerjee A, Baker D, Constantinescu S, Pellegrini S, 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;283:18566-72 pubmed publisher
    ..Here we identify a member of the Janus kinase (Jak) family, Tyk2, as a component of such a masking complex...
  4. Wang K, Zhang H, Kugathasan S, Annese V, Bradfield J, Russell R, et al. Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn Disease. Am J Hum Genet. 2009;84:399-405 pubmed publisher
    ..In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests...
  5. Strange A, Capon F, Spencer C, Knight J, Weale M, Allen M, et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet. 2010;42:985-90 pubmed publisher
    ..Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2)...
  6. 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 ..
  7. Couturier N, Bucciarelli F, Nurtdinov R, Debouverie M, Lebrun Frenay C, Defer G, et al. Tyrosine kinase 2 variant influences T lymphocyte polarization and multiple sclerosis susceptibility. Brain. 2011;134:693-703 pubmed publisher
    ..comparing the reactivity and cytokine profile of T lymphocytes isolated from individuals expressing the protective TYK2(GC) genotype with the disease-associated TYK2(GG) genotype...
  8. Li Z, Gakovic M, Ragimbeau J, Eloranta M, Rönnblom L, Michel F, et al. Two rare disease-associated Tyk2 variants are catalytically impaired but signaling competent. J Immunol. 2013;190:2335-44 pubmed publisher
    b>Tyk2 belongs to the Janus protein tyrosine kinase family and is involved in signaling of immunoregulatory cytokines (type I and III IFNs, IL-6, IL-10, and IL-12 families) via its interaction with shared receptor subunits...
  9. Sohn S, Barrett K, van Abbema A, Chang C, Kohli P, Kanda H, et al. A restricted role for TYK2 catalytic activity in human cytokine responses revealed by novel TYK2-selective inhibitors. J Immunol. 2013;191:2205-16 pubmed publisher
    b>TYK2 is a JAK family protein tyrosine kinase activated in response to multiple cytokines, including type I IFNs, IL-6, IL-10, IL-12, and IL-23...
  10. Wheeler J, Vanoni S, Zeng C, Waggoner L, Yang Y, Wu D, et al. 17β-Estradiol protects the esophageal epithelium from IL-13-induced barrier dysfunction and remodeling. J Allergy Clin Immunol. 2018;: pubmed publisher
    ..Estrogen hormone signaling may protect against development of EoE in female subjects. ..
  11. Chasset F, Arnaud L. Targeting interferons and their pathways in systemic lupus erythematosus. Autoimmun Rev. 2018;17:44-52 pubmed publisher
    ..kinase (Syk), Janus-kinases (JAKs), interleukin-1 receptor-associated kinase 4 (IRAK4), or the Tyrosine Kinase 2 (TYK2) are also investigated actively in SLE, at more preliminary clinical development stages, except for JAK inhibitors ..
  12. Yu Y, Wan P, Cao Y, Zhang W, Chen J, Tan L, et al. Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action. Sci Rep. 2017;7:1729 pubmed publisher
    ..Subsequently, SOCS2 impairs IFN/JAK/STAT signaling through reducing the stability of tyrosine kinase 2 (TYK2), downregulating the expression of type I and III IFN receptors, attenuating the phosphorylation and nucleus ..
  13. Idborg H, Zandian A, Sandberg A, Nilsson B, Elvin K, Truedsson L, et al. Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjögren's syndrome differ in molecular signatures and treatment perspectives. Arthritis Res Ther. 2019;21:62 pubmed publisher
    ..This subgroup was also characterized by a possible activation of the interferon system as measured by high KRT7, TYK2, and ETV7 in plasma...
  14. Brütting C, Emmer A, Kornhuber M, Staege M. A survey of endogenous retrovirus (ERV) sequences in the vicinity of multiple sclerosis (MS)-associated single nucleotide polymorphisms (SNPs). Mol Biol Rep. 2016;43:827-36 pubmed publisher
    ..The associated genes (CYP27B1, CD6, CD58, MPV17L2, IL12RB1, CXCR5, PTGER4, TAGAP, TYK2, ICAM3, CD86, GALC, GPR65 as well as the HLA DRB1*1501) are mainly involved in the immune system, but also in ..
  15. Solus J, Chung C, Oeser A, Li C, Rho Y, Bradley K, et al. Genetics of serum concentration of IL-6 and TNFα in systemic lupus erythematosus and rheumatoid arthritis: a candidate gene analysis. Clin Rheumatol. 2015;34:1375-82 pubmed publisher
    ..Polymorphisms in several genes were associated with IL-6 levels (including IL10, TYK2, and CD40L in SLE and DRB1, NOD2, and CSF1 in RA) or with TNFα levels (including TNFSF4 and CSF2 in SLE and ..
  16. Sullivan K, Lewis H, Hill A, Pandey A, Jackson L, Cabral J, et al. Trisomy 21 consistently activates the interferon response. elife. 2016;5: pubmed publisher
    ..An shRNA screen determined that the interferon-activated kinases JAK1 and TYK2 suppress proliferation of trisomy 21 fibroblasts, and this defect is rescued by pharmacological JAK inhibition...
  17. Wang C, Huang A, Hour M, Huang S, Kung S, Chen C, et al. Antiviral Potential of a Novel Compound CW-33 against Enterovirus A71 via Inhibition of Viral 2A Protease. Viruses. 2015;7:3155-71 pubmed publisher
    ..CW-33 also recovered Type I IFN-induced Tyk2 and STAT1 phosphorylation as well as 2\',5\'-OAS upregulation in EV-A71 infected cells...
  18. Nucci L, Santos S, Brunialti M, Sharma N, Machado F, Assunção M, et al. Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients. PLoS ONE. 2017;12:e0172024 pubmed publisher
    ..The canonical pathways altered in D0 samples included interferon and iNOS signaling; the role of JAK1, JAK2 and TYK2 in interferon signaling; mitochondrial dysfunction; and superoxide radical degradation pathways...
  19. Truong A, Hong Y, Lee J, Lee K, Kil D, Lillehoj H, et al. Interleukin-34 Regulates Th1 and Th17 Cytokine Production by Activating Multiple Signaling Pathways through CSF-1R in Chicken Cell Lines. Int J Mol Sci. 2018;19: pubmed publisher
    ..Th17 cytokines through phosphorylation of tyrosine and serine residues in Janus kinase (JAK) 2, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription (STAT) 1, STAT3, and Src homology 2-containing tyrosine ..
  20. Truong A, Hoang C, Hong Y, Lee J, Lee K, Lillehoj H, et al. Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex. Mol Immunol. 2017;92:54-67 pubmed publisher
    ..In addition, ChIL-23 complex are associated with IL-23R, IL-12R?1 receptors; activate the JAK2/TYK2, STAT1/3, SOCS1 genes, and induced proinflammatory cytokines in immune cells...
  21. Li Z, Yang L, Liu X, Wang X, Pan Y, Luo J. The Long Noncoding RNA MEG3 and its Target miR-147 Regulate JAK/STAT Pathway in Advanced Chronic Myeloid Leukemia. EBioMedicine. 2018;34:61-75 pubmed publisher
    ..We also found MEG3 interacted with DNMT1, JAK2, STAT3, HDAC1, and TYK2, and JAK2 was bound to STAT3, STAT5 and MYC. More interestingly, JAK2 was bound to TYK2 by the bridge of MEG3...
  22. Nguyen H, Noss E, Mizoguchi F, Huppertz C, Wei K, Watts G, et al. Autocrine Loop Involving IL-6 Family Member LIF, LIF Receptor, and STAT4 Drives Sustained Fibroblast Production of Inflammatory Mediators. Immunity. 2017;46:220-232 pubmed publisher
    ..fibroblast activation, and LIF receptor (LIFR) and STAT4 formed a molecular complex that, together with JAK1 and TYK2 kinases, controlled STAT4 activation...
  23. Marroquí L, dos Santos R, Op De Beeck A, Coomans de Brachène A, Marselli L, Marchetti P, et al. Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes. Diabetologia. 2017;60:656-667 pubmed publisher
    ..HLA class I, inflammation and ER stress markers in human beta cells via activation of the candidate gene TYK2, and the transcription factors signal transducer and activator of transcription 2 and IFN regulatory factor 9...
  24. Truong A, Rengaraj D, Hong Y, Hoang C, Hong Y, Lillehoj H. Differentially expressed JAK-STAT signaling pathway genes and target microRNAs in the spleen of necrotic enteritis-afflicted chicken lines. Res Vet Sci. 2017;115:235-243 pubmed publisher
    ..According to the RNA-Seq results, several key genes, including STAT1-6, JAK1-3, TYK2, AKT1, AKT3, SOCS1-5, PIAS1, PIAS2, PIAS4, SHP1, SHP2, and PIK3, showed marked differential expression in the two ..
  25. Reed B, Dolen W. The Child with Recurrent Mycobacterial Disease. Curr Allergy Asthma Rep. 2018;18:44 pubmed publisher
    ..pathways can cause the MSMD phenotype, some of which include IL12RB1, IL12B, IKBKG, ISG15, IFNGR1, IFNGR2, CYBB, TYK2, IRF8, and STAT1...
  26. Floss D, Klöcker T, Schröder J, Lamertz L, Mrotzek S, Strobl B, et al. Defining the functional binding sites of interleukin 12 receptor ?1 and interleukin 23 receptor to Janus kinases. Mol Biol Cell. 2016;27:2301-16 pubmed publisher
    ..Coimmunoprecipitation of Tyk2 by IL-12R?1 and Jak2 by IL?23R supported these findings...
  27. Nenasheva V, Kovaleva G, Uryvaev L, Ionova K, Dedova A, Vorkunova G, et al. Enhanced expression of trim14 gene suppressed Sindbis virus reproduction and modulated the transcription of a large number of genes of innate immunity. Immunol Res. 2015;62:255-62 pubmed publisher
    ..1, akt1, tyk2, erk2, mek2) and lowered transcription of 3 genes (ifnγ, gata1, il-17a)...
  28. Hao Q, Samten B, Ji H, Zhao Z, Tang H. Tyrosine phosphatase PTP-MEG2 negatively regulates vascular endothelial growth factor receptor signaling and function in endothelial cells. Am J Physiol Cell Physiol. 2012;303:C548-53 pubmed publisher
    ..found that PTP-MEG2 DA mutant preferentially associated with Janus kinase 1 (JAK1) but not with other JAK kinases (Tyk2 and JAK2) present in ECs and regulated JAK1 tyrosine phosphorylation...
  29. Wonganan O, He Y, Shen X, Wongkrajang K, Suksamrarn A, Zhang G, et al. 6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiates the anti-proliferative effect of interferon ?/? by promoting activation of the JAK/STAT signaling by inhibiting SOCS3 in hepatocellular carcinoma cells. Toxicol Appl Pharmacol. 2017;336:31-39 pubmed publisher
    ..33±0.04?M. K6G enhanced the phosphorylation of JAK1, Tyk2, and STAT1/2 but decreased the phosphorylation of STAT3...
  30. Elalouf O, Chandran V. Novel Therapeutics in Psoriatic Arthritis. What Is in the Pipeline?. Curr Rheumatol Rep. 2018;20:36 pubmed publisher
    ..selective inhibition of IL 23, therapies promoting activated T cell apoptosis, inhibition of tyrosine kinase 2 (TYK2), and more are under active assessment in ongoing clinical trials...
  31. Emmons T, Wrightstone A, Baima E, Brown S, Sommers C, Hirsch J, et al. Differential kinetics and inhibition of purified recombinant tyrosine kinase 2 (TYK-2) and its catalytic domain JH-1. Protein Pept Lett. 2012;19:485-91 pubmed
    ..Inhibition of TYK-2 autophosphorylation may represent a new area of investigation for the JAK family. ..
  32. Hazari S, Taylor L, Haque S, Garry R, Florman S, Luftig R, et al. Reduced expression of Jak-1 and Tyk-2 proteins leads to interferon resistance in hepatitis C virus replicon. Virol J. 2007;4:89 pubmed
    ..signaling and phosphorylation of STAT 1 and STAT 2 proteins were strongly inhibited due to reduced expression of Tyk2 and Jak-1 protein...
  33. Santos J, Mesquita D, Barros Silva J, Jerónimo C, Henrique R, Morais A, et al. Uncovering potential downstream targets of oncogenic GRPR overexpression in prostate carcinomas harboring ETS rearrangements. Oncoscience. 2015;2:497-507 pubmed
    ..antibody microarray we were able to validate known and identify new targets of GRPR pathway, namely AKT1, PKCε, TYK2 and MST1...
  34. Mazdeh M, Moradi N, Khoshroo E, Shayesteh Z, Taheri M, Sayad A, et al. Down-regulation of TYK2, CBLB and LMP7 genes expression in relapsing-remitting multiple sclerosis patients treated with interferon-beta. J Neuroimmunol. 2018;314:24-29 pubmed publisher
    This study aimed to examine the expression of TYK2, CBLB and LMP7 genes at both mRNA and protein levels in relapsing-remitting MS (RRMS) patients in compare with healthy controls...
  35. Patecki M, von Schaewen M, Tkachuk S, Jerke U, Dietz R, Dumler I, et al. Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth. Biochem Biophys Res Commun. 2007;359:679-84 pubmed
    ..We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury...
  36. Mero I, Lorentzen A, Ban M, Smestad C, Celius E, Aarseth J, et al. A rare variant of the TYK2 gene is confirmed to be associated with multiple sclerosis. Eur J Hum Genet. 2010;18:502-4 pubmed publisher
    A rare functional variant within the TYK2 gene (rs34536443) has been reported as protective in multiple sclerosis (MS) in recent studies. However, because of the low frequency of the minor allele (minor allele frequency=0...
  37. Ehm M, Aponte J, Chiano M, Yerges Armstrong L, Johnson T, Barker J, et al. Phenome-wide association study using research participants' self-reported data provides insight into the Th17 and IL-17 pathway. PLoS ONE. 2017;12:e0186405 pubmed publisher
    ..Ile684Ser in TYK2 with increased risk of tonsillectomy, strep throat occurrences and teen acne, the variant encoding p...
  38. Omede A, Zi M, Prehar S, Maqsood A, Stafford N, Mamas M, et al. The oxoglutarate receptor 1 (OXGR1) modulates pressure overload-induced cardiac hypertrophy in mice. Biochem Biophys Res Commun. 2016;479:708-714 pubmed publisher
    ..Since CSN5 interacts with TYK2, a major upstream regulator of STAT3, OXGR1 might regulate the pro-hypertrophic STAT3 pathway via interaction with ..
  39. 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 ..
  40. Ibrahim H, Askar B, Barrow P, Foster N. Dysregulation of JAK/STAT genes by vasoactive intestinal peptide (VIP) in Salmonella-infected monocytes may inhibit its therapeutic potential in human sepsis. Cytokine. 2018;105:49-56 pubmed publisher
    ..05). S. Typhimurium 14028 also increased expression of PTPN1, which dephosphorylates JAK2 and TYK2. This was unaltered by co-culture with VIP but S...
  41. Jang W, Kim J, Son H, Park S, Cho Y, Koo T, et al. Discovery of Tyk2 inhibitors via the virtual site-directed fragment-based drug design. Bioorg Med Chem Lett. 2015;25:3947-52 pubmed publisher
    In this study, we synthesized compound 12 with potent Tyk2 inhibitory activity from FBDD study and carried out a cell-based assay for Tyk2/STAT3 signaling activation upon IFNα5 stimulation...
  42. Sukhov A, Adamopoulos I, Maverakis E. Interactions of the Immune System with Skin and Bone Tissue in Psoriatic Arthritis: A Comprehensive Review. Clin Rev Allergy Immunol. 2016;51:87-99 pubmed publisher
    ..susceptibility loci (LCE3, CARD14, NOS2, NFKBIA, PSMA6, ERAP1, TRAF3IP2, IL12RB2, IL23R, IL12B, TNIP1, TNFAIP3, TYK2) and geoepidemiologic factors that contribute to the wide variability seen in psoriasis...
  43. 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...
  44. Hellquist A, Järvinen T, Koskenmies S, Zucchelli M, Orsmark Pietras C, Berglind L, et al. Evidence for genetic association and interaction between the TYK2 and IRF5 genes in systemic lupus erythematosus. J Rheumatol. 2009;36:1631-8 pubmed publisher
    ..Our aim was to systematically replicate 6 such genes, TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2...
  45. 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 preadipocytes both ..
  46. Johnson B, Wang J, Taylor E, Caillier S, Herbert J, Khan O, et al. Multiple sclerosis susceptibility alleles in African Americans. Genes Immun. 2010;11:343-50 pubmed publisher
    ..CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set...
  47. Peng H, Cheng Y, Hsu Y, Wu G, Kuo C, Liou J, et al. MPT0B098, a Microtubule Inhibitor, Suppresses JAK2/STAT3 Signaling Pathway through Modulation of SOCS3 Stability in Oral Squamous Cell Carcinoma. PLoS ONE. 2016;11:e0158440 pubmed publisher
    ..The accumulation of SOCS3 protein enhanced its binding to JAK2 and TYK2 which facilitated the ubiquitination and degradation of JAK2 and TYK2, resulting in a loss of STAT3 activity...
  48. Ma C, Wong N, Rao G, Nguyen A, Avery D, Payne K, et al. Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets. J Exp Med. 2016;213:1589-608 pubmed publisher
    ..IL12R?1/TYK2 and IFN-?R/STAT1 function in a feed-forward loop to induce Th1 cells, whereas IL-21/IL-21R/STAT3 signaling is ..
  49. Yang C, Murti A, Valentine W, Du Z, Pfeffer L. Interferon alpha activates NF-kappaB in JAK1-deficient cells through a TYK2-dependent pathway. J Biol Chem. 2005;280:25849-53 pubmed
    ..Expression of a catalytically inactive TYK2 tyrosine kinase in JAK1-deficient cells, as well as in the highly IFN-sensitive Daudi lymphoblastoid cell line, ..
  50. Li L, Chen S, Wang Q, Wu C, Wen X, Yang F, et al. GLIS3 and TYK2 Single Nucleotide Polymorphisms Are Not Associated with Dermatomyositis/Polymyositis in Chinese Han Population. Genet Test Mol Biomarkers. 2017;21:565-570 pubmed publisher
    ..Single nucleotide polymorphisms (SNPs) in the GLI-similar 3 (GLIS3) and tyrosine kinase 2 (TYK2) genes have been associated with various autoimmune diseases...
  51. Gauzzi M, Velazquez L, McKendry R, Mogensen K, Fellous M, Pellegrini S. Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase. J Biol Chem. 1996;271:20494-500 pubmed
    b>Tyk2 and JAK1, members of the Janus kinase (JAK) family of protein tyrosine kinases, are required for interferon-alpha/beta binding and signaling...
  52. Kim H, Baumann H. Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells. J Biol Chem. 1997;272:30741-7 pubmed
    ..Bcr/gp130 is capable of interacting with JAK1, JAK2, and TYK2; is constitutively active; and induces gene expression through IL-6-responsive elements...
  53. Su Q, Wang S, Baltzis D, Qu L, Raven J, Li S, et al. Interferons induce tyrosine phosphorylation of the eIF2alpha kinase PKR through activation of Jak1 and Tyk2. EMBO Rep. 2007;8:265-70 pubmed
    ..We show that PKR physically interacts with either Jak1 or Tyk2 in unstimulated cells and that these interactions are increased in IFN-treated cells...
  54. Welzel T, Morgan T, Bonkovsky H, Naishadham D, Pfeiffer R, Wright E, et al. Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial. Hepatology. 2009;49:1847-58 pubmed publisher
    ..66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2-2256A promoter region variant, a borderline association was present among European American participants (OR, 1...
  55. Nititham J, Gupta R, Zeng X, Hartogensis W, Nixon D, Deeks S, et al. Psoriasis risk SNPs and their association with HIV-1 control. Hum Immunol. 2017;78:179-184 pubmed publisher
    ..A number of genetic variants outside the MHC (SOX5, TLR9, SDC4, PROX1, IL12B, TLR4, MBL-2, TYK2, IFIH1) demonstrated nominal significance...
  56. Usacheva A, Tian X, Sandoval R, Salvi D, Levy D, Colamonici O. The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex. J Immunol. 2003;171:2989-94 pubmed
    ..Finally, we provide evidence that RACK-1 may also serve as a scaffold protein in other cytokine systems such as IL-2, IL-4, and erythropoietin. ..
  57. Novak U, Harpur A, Paradiso L, Kanagasundaram V, Jaworowski A, Wilks A, et al. Colony-stimulating factor 1-induced STAT1 and STAT3 activation is accompanied by phosphorylation of Tyk2 in macrophages and Tyk2 and JAK1 in fibroblasts. Blood. 1995;86:2948-56 pubmed
    ..The activation of the STAT proteins in BMM is accompanied by tyrosine phosphorylation of Tyk2. In fibroblasts, the activation of the STAT proteins is accompanied by tyrosine phosphorylation of Tyk2 and JAK1...
  58. Sigurdsson S, Nordmark G, Goring H, Lindroos K, Wiman A, Sturfelt G, et al. Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Genet. 2005;76:528-37 pubmed
    ..In two of the genes--the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes--we identified SNPs that displayed strong signals in joint analysis of ..
  59. Alves de Medeiros A, Speeckaert R, Desmet E, Van Gele M, De Schepper S, Lambert J. JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases. PLoS ONE. 2016;11:e0164080 pubmed publisher
    ..AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature...
  60. Calama E, Ramis I, Domènech A, Carreño C, De Alba J, Prats N, et al. Tofacitinib ameliorates inflammation in a rat model of airway neutrophilia induced by inhaled LPS. Pulm Pharmacol Ther. 2017;43:60-67 pubmed publisher
    ..Four JAK proteins, JAK1, JAK2, JAK3 and tyrosine kinase 2 (Tyk2) associate with the intracellular domains of surface cytokine receptors are phosphorylating STATs and modulating ..
  61. Vignais M, Sadowski H, Watling D, Rogers N, Gilman M. Platelet-derived growth factor induces phosphorylation of multiple JAK family kinases and STAT proteins. Mol Cell Biol. 1996;16:1759-69 pubmed
    ..Here, we show that all three of the ubiquitously expressed JAKs--JAK1, JAK2, and Tyk2--become phosphorylated on tyrosine in both mouse BALB/c 3T3 cells and human fibroblasts engineered to express the ..
  62. Miyakawa Y, Oda A, Druker B, Ozaki K, Handa M, Ohashi H, et al. Thrombopoietin and thrombin induce tyrosine phosphorylation of Vav in human blood platelets. Blood. 1997;89:2789-98 pubmed
    ..human platelets and recently demonstrated that thrombopoietin induces rapid tyrosine phosphorylation of Jak-2, Tyk2, Shc, Stat3, Stat5, p120(c-cbl) and other proteins in human platelets...
  63. Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, et al. STAM2, a new member of the STAM family, binding to the Janus kinases. FEBS Lett. 2000;477:55-61 pubmed
  64. Shide K, Shimoda K, Kamezaki K, Kakumitsu H, Kumano T, Numata A, et al. Tyk2 mutation homologous to V617F Jak2 is not found in essential thrombocythaemia, although it induces constitutive signaling and growth factor independence. Leuk Res. 2007;31:1077-84 pubmed
    ..As valine 617 of Jak2 is conserved as valine 678 of Tyk2, we examined the effect of a homologous mutation in Tyk2 (V678F Tyk2) on cell growth...
  65. Li P, Chang Y, Shek K, Lau Y. Lack of association of TYK2 gene polymorphisms in Chinese patients with systemic lupus erythematosus. J Rheumatol. 2011;38:177-8 pubmed publisher
  66. Ren J, Kolli D, Liu T, Xu R, Garofalo R, Casola A, et al. Human metapneumovirus inhibits IFN-? signaling by downregulating Jak1 and Tyk2 cellular levels. PLoS ONE. 2011;6:e24496 pubmed publisher
    ..airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2), due to enhanced proteosomal degradation and reduced gene transcription...
  67. Herrmann A, Lahtz C, Nagao T, Song J, Chan W, Lee H, et al. CTLA4 Promotes Tyk2-STAT3-Dependent B-cell Oncogenicity. Cancer Res. 2017;77:5118-5128 pubmed publisher
    ..CTLA4-CD86 ligation recruited and activated the JAK family member Tyk2, resulting in STAT3 activation and expression of genes critical for cancer immunosuppression and tumor growth and ..
  68. Dumler I, Weis A, Mayboroda O, Maasch C, Jerke U, Haller H, et al. The Jak/Stat pathway and urokinase receptor signaling in human aortic vascular smooth muscle cells. J Biol Chem. 1998;273:315-21 pubmed
    ..uPAR-associated proteins were identified as Janus (Jak) and Src non-receptor protein-tyrosine kinases (PTK) Jak1, Tyk2, and p59(fyn), p53/56(lyn), p53/59(hck), and p55(fgr)...
  69. Kusch A, Tkachuk S, Haller H, Dietz R, Gulba D, Lipp M, et al. Urokinase stimulates human vascular smooth muscle cell migration via a phosphatidylinositol 3-kinase-Tyk2 interaction. J Biol Chem. 2000;275:39466-73 pubmed
    Janus kinases Jak1 and Tyk2 play an important role in urokinase-type plasminogen activator (uPA)-dependent signaling...
  70. Uddin S, Sassano A, Deb D, Verma A, Majchrzak B, Rahman A, et al. Protein kinase C-delta (PKC-delta ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. J Biol Chem. 2002;277:14408-16 pubmed
    ..Altogether, these findings indicate that PKC-delta functions as a serine kinase for Stat1 and an upstream regulator of the p38 MAP kinase and plays an important role in the induction of Type I IFN-biological responses. ..
  71. Doucet C, Giron Michel J, Canonica G, Azzarone B. Human lung myofibroblasts as effectors of the inflammatory process: the common receptor gamma chain is induced by Th2 cytokines, and CD40 ligand is induced by lipopolysaccharide, thrombin and TNF-alpha. Eur J Immunol. 2002;32:2437-49 pubmed
    ..Treatment with JAK3 inhibitors blocks IL-13-induced phosphorylation of JAK2, TYK2 and STAT3, but not of JAK1 and STAT6...
  72. Kiian I, Tkachuk N, Haller H, Dumler I. Urokinase-induced migration of human vascular smooth muscle cells requires coupling of the small GTPases RhoA and Rac1 to the Tyk2/PI3-K signalling pathway. Thromb Haemost. 2003;89:904-14 pubmed
    ..cell (VSMC) uPA stimulates migration via the uPA receptor (uPAR) signalling complex containing the Janus kinase Tyk2 and phosphatidylinositol 3-kinase (PI3-K)...
  73. Staerk J, Kallin A, Demoulin J, Vainchenker W, Constantinescu S. JAK1 and Tyk2 activation by the homologous polycythemia vera JAK2 V617F mutation: cross-talk with IGF1 receptor. J Biol Chem. 2005;280:41893-9 pubmed
    ..Here we show that the homologous mutations in JAK1 (V658F) and in Tyk2 (V678F) lead to constitutive activation of these kinases...
  74. Schischmanoff P, Naccache J, Carrere A, Richardson S, Kambouchner M, Raphael M, et al. Progressive pulmonary sarcoidosis is associated with over-expression of TYK2 and p21Waf1/Cip1. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23:101-7 pubmed
    ..sarcoidosis including three genes coding for effectors of the Th1 immune response: the protein tyrosine kinase TYK2, the Interferon-gamma receptor 2 and the cell cycle inhibitor p21Waf1/Cip1...
  75. . Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet. 2009;41:824-8 pubmed publisher
    ..6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).
  76. 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
    ..Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which inhibited ..
  77. Liu J, Almarri M, Gaffney D, Mells G, Jostins L, Cordell H, et al. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nat Genet. 2012;44:1137-41 pubmed publisher
    ..The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis...
  78. Liang Y, Zhu Y, Xia Y, Peng H, Yang X, Liu Y, et al. Therapeutic potential of tyrosine kinase 2 in autoimmunity. Expert Opin Ther Targets. 2014;18:571-80 pubmed publisher
    Tyrosine kinase 2 (Tyk2) is a Janus kinase family member that is crucial for signaling transduction in response to a wide variety of cytokines, including type I IFNs, IL-6, IL-10, IL-12 and IL-23...
  79. Tron A, Keeton E, Ye M, Casás Selves M, Chen H, Dillman K, et al. Next-generation sequencing identifies a novel ELAVL1-TYK2 fusion gene in MOLM-16, an AML cell line highly sensitive to the PIM kinase inhibitor AZD1208. Leuk Lymphoma. 2016;57:2927-2929 pubmed
  80. Trask B, Fertitta A, Christensen M, Youngblom J, Bergmann A, Copeland A, et al. Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers. Genomics. 1993;15:133-45 pubmed
    ..FISH mapping of these cosmids sublocalizes a total of 70 genes and DNA markers on chromosome 19, revises the previously published map assignments of 2 genes, and narrows the location of over 20 markers. ..
  81. Ahmad S, Alsayed Y, Druker B, Platanias L. The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein. J Biol Chem. 1997;272:29991-4 pubmed
    ..Thus, tyrosine phosphorylation of CrkL links the functional Type I IFNR complex to the C3G-Rap-1 signaling cascade that mediates growth inhibitory responses. ..
  82. Uddin S, Grumbach I, Yi T, Colamonici O, Platanias L. Interferon alpha activates the tyrosine kinase Lyn in haemopoietic cells. Br J Haematol. 1998;101:446-9 pubmed
    ..Thus, during binding of IFN alpha to its receptor in malignant haemopoietic cells, Lyn is engaged in an IFN alpha-signalling pathway, probably downstream of Tyk-2. ..
  83. Roy B, Cathcart M. Induction of 15-lipoxygenase expression by IL-13 requires tyrosine phosphorylation of Jak2 and Tyk2 in human monocytes. J Biol Chem. 1998;273:32023-9 pubmed
    ..and antiphosphotyrosine blotting experiments, IL-13 was shown to induce tyrosine phosphorylation of Jak2 and Tyk2, but not Jak1 or Jak3, within 5 min of treatment in human monocytes...
  84. Dumler I, Kopmann A, Weis A, Mayboroda O, Wagner K, Gulba D, et al. Urokinase activates the Jak/Stat signal transduction pathway in human vascular endothelial cells. Arterioscler Thromb Vasc Biol. 1999;19:290-7 pubmed
    ..the activated urokinase receptor is associated with 2 cytoplasmic tyrosine kinases of the Jak family, viz, Jak1 and Tyk2. uPA and ATF induced a time-dependent activation of both kinases, as shown by immunoprecipitation and Western blot ..
  85. Orchansky P, Kwan R, Lee F, Schrader J. Characterization of the cytoplasmic domain of interleukin-13 receptor-alpha. J Biol Chem. 1999;274:20818-25 pubmed
    ..The cytoplasmic domain of IL-13Ralpha was constitutively associated with STAT3, Tyk2, and Janus kinase 1 (JAK1)...
  86. Wang F, Barrett J, Shao Q, Gao X, Dekaban G, McFadden G. Myxoma virus selectively disrupts type I interferon signaling in primary human fibroblasts by blocking the activation of the Janus kinase Tyk2. Virology. 2009;387:136-46 pubmed publisher
    ..IFN is added to primary human fibroblasts following MV infection, the tyrosine phosphorylation of the Janus kinase Tyk2 is specifically blocked, thereby preventing the subsequent activation of downstream STAT1 and STAT2...
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    ..We compared 17 single nucleotide polymorphisms (SNPs) at IFNAR1, IFNAR2, JAK1, TYK2, STAT1, STAT3 and STAT5a/b between the two groups and found a significant difference for rs6503691, a SNP tightly ..
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    Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family of nonreceptor tyrosine kinases, which are essential for proper signaling in immune responses and development. Here we present a 2...
  89. Jani M, Massey J, Wedderburn L, Vencovsky J, Danko K, Lundberg I, et al. Genotyping of immune-related genetic variants identifies TYK2 as a novel associated locus for idiopathic inflammatory myopathies. Ann Rheum Dis. 2014;73:1750-2 pubmed publisher
  90. Mine K, Hirakawa K, Kondo S, Minami M, Okada A, Tsutsu N, et al. Subtyping of Type 1 Diabetes as Classified by Anti-GAD Antibody, IgE Levels, and Tyrosine kinase 2 (TYK2) Promoter Variant in the Japanese. EBioMedicine. 2017;23:46-51 pubmed publisher
    Type 1 diabetes (T1D) is known to be caused by Th1 cell-dependent autoimmunity. Recently, we reported that TYK2 promoter variant serves as a putative virus-induced diabetes susceptibility gene associated with deteriorated interferon-..
  91. Partanen J, Mäkelä T, Alitalo R, Lehvaslaiho H, Alitalo K. Putative tyrosine kinases expressed in K-562 human leukemia cells. Proc Natl Acad Sci U S A. 1990;87:8913-7 pubmed
    ..chain reaction-amplified cDNA clones led to the identification of 14 different tyrosine kinase-related sequences (JTK1-14)...
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