Gene Symbol: Jak1
Description: Janus kinase 1
Alias: JAK1A, JAK1B, JTK3, tyrosine-protein kinase JAK1
Species: human
Products:     Jak1

Top Publications

  1. Seki Y, Hayashi K, Matsumoto A, Seki N, Tsukada J, Ransom J, et al. Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation. Proc Natl Acad Sci U S A. 2002;99:13003-8 pubmed
    ..Therefore, the induced SOCS5 protein in Th1 differentiation environment may play an important role by regulating Th1 and Th2 balance. ..
  2. 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
    ..This finding shows that tyk2 links the interferon alpha/beta receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes. ..
  3. Haan C, Is harc H, Hermanns H, Schmitz Van de Leur H, Kerr I, Heinrich P, et al. Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction. J Biol Chem. 2001;276:37451-8 pubmed
    Janus kinase 1 (Jak1) is a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors...
  4. Leonard W, O Shea J. Jaks and STATs: biological implications. Annu Rev Immunol. 1998;16:293-322 pubmed
    ..STATs then can modulate the expression of target genes. The basic biology of this system, including the range of known Jaks and STATs, is discussed, as are the defects in animals and humans lacking some of these signaling molecules. ..
  5. Zhang W, Wang L, Wang Q, Luo X, Fang D, Chen Y, et al. CUEDC2 (CUE domain-containing 2) and SOCS3 (suppressors of cytokine signaling 3) cooperate to negatively regulate Janus kinase 1/signal transducers and activators of transcription 3 signaling. J Biol Chem. 2012;287:382-92 pubmed publisher
    Janus kinase 1/signal transducers and activators of transcription 3 (JAK1/STAT3) pathway is one of the recognized oncogenic signaling pathways that frequently overactivated in a variety of human tumors...
  6. Gordon G, Lambert Q, Daniel K, Reuther G. Transforming JAK1 mutations exhibit differential signalling, FERM domain requirements and growth responses to interferon-?. Biochem J. 2010;432:255-65 pubmed publisher
    ..Although sequencing efforts have uncovered transforming JAK1 mutations in acute leukaemia, they have also identified non-transforming JAK1 mutations...
  7. Nicholson S, Oates A, Harpur A, Ziemiecki A, Wilks A, Layton J. Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation. Proc Natl Acad Sci U S A. 1994;91:2985-8 pubmed
    ..We detected tyrosine phosphorylation of both the G-CSF receptor and the protein tyrosine kinase JAK1 following G-CSF binding to the human G-CSF receptor...
  8. Muller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, et al. The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. Nature. 1993;366:129-35 pubmed
    We have produced a cell line which lacks the protein tyrosine kinase JAK1 and is completely defective in interferon response...
  9. Haan S, Margue C, Engrand A, Rolvering C, Schmitz Van de Leur H, Heinrich P, et al. Dual role of the Jak1 FERM and kinase domains in cytokine receptor binding and in stimulation-dependent Jak activation. J Immunol. 2008;180:998-1007 pubmed
    b>Jak1 is a tyrosine kinase that noncovalently forms tight complexes with a variety of cytokine receptors and is critically involved in signal transduction via cytokines. Jaks are predicted to have a 4...

More Information

Publications125 found, 100 shown here

  1. Rodriguez Frade J, Vila Coro A, Martin A, Nieto M, Sanchez Madrid F, Proudfoot A, et al. Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: implications for chemotaxis. J Cell Biol. 1999;144:755-65 pubmed
    ..The results are discussed in the context of the dissociation of the late signals, provoked by the chemokines required for cell migration, from early signals. ..
  2. 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. ..
  3. Radtke S, Haan S, Jörissen A, Hermanns H, Diefenbach S, Smyczek T, et al. The Jak1 SH2 domain does not fulfill a classical SH2 function in Jak/STAT signaling but plays a structural role for receptor interaction and up-regulation of receptor surface expression. J Biol Chem. 2005;280:25760-8 pubmed
    ..We performed an in depth study to determine the function of the Jak1 SH2 domain...
  4. Rodig S, Meraz M, White J, Lampe P, Riley J, Arthur C, et al. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell. 1998;93:373-83 pubmed
    Herein we report the generation of mice lacking the ubiquitously expressed Janus kinase, Jak1. Jak1-/- mice are runted at birth, fail to nurse, and die perinatally...
  5. Sporri B, Kovanen P, Sasaki A, Yoshimura A, Leonard W. JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling. Blood. 2001;97:221-6 pubmed
    ..In cotransfection experiments, JAB/SOCS1/SSI-1 associates with both Jak1 and Jak3; however, JAB/SOCS1/SSI-1 had a greater effect on Jak1 tyrosine phosphorylation and kinase activity...
  6. Demoulin J, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J, et al. A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9. Mol Cell Biol. 1996;16:4710-6 pubmed
    ..tyrosine phosphorylation of the receptor and for STAT activation but not for IRS-2/4PS activation or for JAK1 phosphorylation, which depended on a domain closer to the plasma membrane...
  7. Yokota S, Saito H, Kubota T, Yokosawa N, Amano K, Fujii N. Measles virus suppresses interferon-alpha signaling pathway: suppression of Jak1 phosphorylation and association of viral accessory proteins, C and V, with interferon-alpha receptor complex. Virology. 2003;306:135-46 pubmed
    ..In the IFN-alpha signal transduction pathway, Jak1 phosphorylation induced by IFN-alpha is dramatically suppressed in MeV-infected cells; however, phosphorylation ..
  8. Rossi M, Hawthorn L, Platt J, Burkhardt T, Cowell J, Ionov Y. Identification of inactivating mutations in the JAK1, SYNJ2, and CLPTM1 genes in prostate cancer cells using inhibition of nonsense-mediated decay and microarray analysis. Cancer Genet Cytogenet. 2005;161:97-103 pubmed
    ..Two different heterozygous mutations in the Janus kinase 1 (JAK1) gene result in complete loss of the protein in several different prostate cancer cell lines.
  9. Breher Esch S, Sahini N, Trincone A, Wallstab C, Borlak J. Genomics of lipid-laden human hepatocyte cultures enables drug target screening for the treatment of non-alcoholic fatty liver disease. BMC Med Genomics. 2018;11:111 pubmed publisher
    ..and fusion and confocal immunofluorescence microscopy evidenced induced LD-associated PLIN2, CIDEC, HIF1α, HILPDA, JAK1, PDK4 and ROCK2 expression...
  10. Jagadeeshan S, David D, Jisha S, Manjula S, Asha Nair S. Solanum nigrum Unripe fruit fraction attenuates Adriamycin resistance by down-regulating multi-drug resistance protein (Mdr)-1 through Jak-STAT pathway. BMC Complement Altern Med. 2017;17:370 pubmed publisher
    ..To elucidate the relationship between SNME and multi drug resistance, we analyzed the expression levels of Mdr-1, JAK1, STAT3, and pSTAT3 in NCI/ADR-RES cells after treatment with SNME...
  11. Liu H, Antony S, Roy K, Juhasz A, Wu Y, Lu J, et al. Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation of human colon cancer cells. Oncotarget. 2017;8:38113-38135 pubmed publisher
    ..Increased NOX1 transcription following IL-4/IL-13 exposure was mediated by JAK1/STAT6 signaling, was associated with a ROS-related inhibition of protein tyrosine phosphatase activity, and was ..
  12. Fang Y, Ning A, Li S, Zhou S, Liu L, Joseph T, et al. Polysaccharides Extracted from Rhizoma Pleionis Have Antitumor Properties In Vitro and in an H22 Mouse Hepatoma Ascites Model In Vivo. Int J Mol Sci. 2018;19: pubmed publisher
    ..PRP induced tumor cell apoptosis by inhibiting the Jak1?Stat3 pathway and by activating Caspase-3 and Caspase-8 to increase the Bax/Bcl-2 ratio...
  13. Bose P, Verstovsek S. Developmental Therapeutics in Myeloproliferative Neoplasms. Clin Lymphoma Myeloma Leuk. 2017;17S:S43-S52 pubmed publisher
    ..JAK inhibitors with potential for less myelosuppression or even improvement of anemia, greater selectivity for JAK1 or JAK2, and the ability to overcome JAK inhibitor persistence are in various stages of development...
  14. Bamidele A, Svingen P, Sagstetter M, Sarmento O, González M, Braga Neto M, et al. Disruption of FOXP3-EZH2 Interaction Represents a Pathobiological Mechanism in Intestinal Inflammation. Cell Mol Gastroenterol Hepatol. 2019;7:55-71 pubmed publisher
    ..Destabilized FOXP3-EZH2 protein interaction via diverse mechanisms and consequent Treg abnormality may drive gastrointestinal inflammation. ..
  15. Hasselbalch H, Holmström M. Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms: minimal residual disease and cure?. Semin Immunopathol. 2019;41:5-19 pubmed publisher
    ..in MPNs is discussed in the context of combination therapies with potent anti-inflammatory agents, such as the JAK1-2 inhibitors (licensed only ruxolitinib) and statins as well...
  16. Zhang H, Watanabe R, Berry G, Tian L, Goronzy J, Weyand C. Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Medium and Large Vessel Vasculitis. Circulation. 2018;137:1934-1948 pubmed publisher
    ..are sensitive to the cytokine-signaling inhibitor tofacitinib, a Janus kinase (JAK) inhibitor targeting JAK3 and JAK1. Vascular inflammation was induced in human arteries engrafted into immunodeficient mice that were reconstituted ..
  17. Bienkowska Haba M, Luszczek W, Keiffer T, Guion L, DiGiuseppe S, Scott R, et al. Incoming human papillomavirus 16 genome is lost in PML protein-deficient HaCaT keratinocytes. Cell Microbiol. 2017;19: pubmed publisher
    ..Abrogation of JAK1/2 signaling prevented genome loss, however, did not restore viral transcription...
  18. Bhattacharjee A, Shukla M, Yakubenko V, Mulya A, Kundu S, Cathcart M. IL-4 and IL-13 employ discrete signaling pathways for target gene expression in alternatively activated monocytes/macrophages. Free Radic Biol Med. 2013;54:1-16 pubmed publisher
    ..activated after the recruitment of IL-13 to its receptor (containing IL-4Rα and IL-13Rα1), IL-4 stimulates Jak1 activation...
  19. Dixon B, Chen D, Zhang Y, Flores J, Malaguit J, Nowrangi D, et al. Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy. ASN Neuro. 2016;8: pubmed
    ..Also an intraperitoneal administration of human recombinant IFN? into the systemic compartment was unable to confer the same protective effects as intranasal IFN? treatment. ..
  20. 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 ..
  21. Wang J, Lu L, Wang Y, Wu Y, Han J, Wang W, et al. Qishenyiqi Dropping Pill attenuates myocardial fibrosis in rats by inhibiting RAAS-mediated arachidonic acid inflammation. J Ethnopharmacol. 2015;176:375-84 pubmed publisher
    ..Expressions of the important signal-transuding proteins, including NF-κB, JAK1/STAT3 and Akt, all increased remarkably in the model group...
  22. Pozdnyakova O, Hasserjian R, Verstovsek S, Orazi A. Impact of bone marrow pathology on the clinical management of Philadelphia chromosome-negative myeloproliferative neoplasms. Clin Lymphoma Myeloma Leuk. 2015;15:253-61 pubmed publisher
    ..In randomized controlled phase 3 studies, the JAK1/JAK2 inhibitor ruxolitinib provided rapid and lasting improvement in MF-related splenomegaly and symptom burden as ..
  23. Khan I, Perrard X, Brunner G, Lui H, Sparks L, Smith S, et al. Intermuscular and perimuscular fat expansion in obesity correlates with skeletal muscle T cell and macrophage infiltration and insulin resistance. Int J Obes (Lond). 2015;39:1607-18 pubmed publisher
    ..cytokine interferon-γ, in SM and adipose tissue inflammation and insulin resistance, mice were treated with a JAK1/JAK2 inhibitor, baricitinib...
  24. Xu Q, Yuan S, Tao Q, Yu J, Cai J, Yang Y, et al. A novel HBx genotype serves as a preoperative predictor and fails to activate the JAK1/STATs pathway in hepatocellular carcinoma. J Hepatol. 2019;70:904-917 pubmed publisher
    ..It also fails to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3)/STAT5 pathway...
  25. Mapes J, Li Q, Kannan A, Anandan L, Laws M, Lydon J, et al. CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy. PLoS Genet. 2017;13:e1006654 pubmed publisher
    ..Proteomic studies further revealed that CUZD1 interacts with a complex containing JAK1/JAK2 and STAT5, downstream transducers of prolactin signaling in the mammary gland...
  26. Barbui T, Tefferi A, Vannucchi A, Passamonti F, Silver R, Hoffman R, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32:1057-1069 pubmed publisher
    ..Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have ..
  27. Guo F, Tang L, Shu S, Sehgal M, Sheraz M, Liu B, et al. Activation of Stimulator of Interferon Genes in Hepatocytes Suppresses the Replication of Hepatitis B Virus. Antimicrob Agents Chemother. 2017;61: pubmed publisher
    ..Hence, despite not playing a significant role in host innate immune response to HBV infection of hepatocytes, STING is potentially a valuable target for immunotherapy of chronic hepatitis B. ..
  28. Wang E, Han Y, Jia X. PAFR-deficiency alleviates myocardial ischemia/reperfusion injury in mice via suppressing inflammation, oxidative stress and apoptosis. Biochem Biophys Res Commun. 2018;495:2475-2481 pubmed publisher
    ..And the activation of Janus kinase 1-signal transducer and activator of transcription 1 (JAK1/STAT1) pathway was also suppressed by PAFR-knockout...
  29. Xiang Z, Zhao Y, Mitaksov V, Fremont D, Kasai Y, Molitoris A, et al. Identification of somatic JAK1 mutations in patients with acute myeloid leukemia. Blood. 2008;111:4809-12 pubmed
    ..diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described...
  30. Luo Q, Wang C, Jin G, Gu D, Wang N, Song J, et al. LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway. Carcinogenesis. 2015;36:1201-12 pubmed publisher
    ..Murine Thymoma Viral Oncogene Homolog (PI3K/AKT) signaling through enhancing phosphorylation of Janus kinase 1 (JAK1), which successively promoted matrix metalloproteinase 13 (MMP13) expression and HCC metastasis...
  31. Lopez Rodriguez R, Hernández Bartolomé Á, Borque M, Rodríguez Muñoz Y, Martín Vílchez S, Garcia Buey L, et al. Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C. PLoS ONE. 2017;12:e0180927 pubmed publisher
    ..Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were ..
  32. Shen T, Chen Z, Zhao Z, Wu J. Genetic defects of the IRF1-mediated major histocompatibility complex class I antigen presentation pathway occur prevalently in the JAK2 gene in non-small cell lung cancer. Oncotarget. 2017;8:60975-60986 pubmed publisher
    ..Loss-of-function (LOF) genetic alterations of the IFN?-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6.3%) of 1,016 patients...
  33. Lo R, Cheung H, Wong Y. Constitutively active Galpha16 stimulates STAT3 via a c-Src/JAK- and ERK-dependent mechanism. J Biol Chem. 2003;278:52154-65 pubmed
    ..Demonstration of the involvement of different kinases in Galpha16QL-induced STAT3 activation supports the involvement of multiple signaling pathways in the regulation of transcription by G proteins. ..
  34. Thomas S, Fisher K, Snowden J, Danson S, Brown S, Zeidler M. Effect of methotrexate on JAK/STAT pathway activation in myeloproliferative neoplasms. Lancet. 2015;385 Suppl 1:S98 pubmed publisher
    ..These results are particularly relevant in myelofibrosis. Inhibitors of JAK1/2 improve symptoms and prolong life in myelofibrosis, but their use is limited by cost...
  35. Yamahata H, Osuka K, Aoyama T, Yasuda M, Tokimura H, Arita K, et al. Expression of the JAK/STAT signaling pathway in the ligamentum flavum of patients with lumbar spinal canal stenosis. J Orthop Sci. 2017;22:190-196 pubmed publisher
    ..The LF of 10 LSS patients was analyzed and the expression of JAK1, STAT3, phosphorylated (p)-STAT3, and actin was examined by Western blot analysis...
  36. Li Y, Buijs Gladdines J, Canté Barrett K, Stubbs A, Vroegindeweij E, Smits W, et al. IL-7 Receptor Mutations and Steroid Resistance in Pediatric T cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study. PLoS Med. 2016;13:e1002200 pubmed publisher
    ..Our analysis revealed that mutations in JAK1 and KRAS, two genes encoding components of the interleukin 7 receptor (IL7R) signaling pathway, were associated ..
  37. Ito M, Yamazaki S, Yamagami K, Kuno M, Morita Y, Okuma K, et al. A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model. J Pharmacol Sci. 2017;133:25-33 pubmed publisher
    The Janus kinase (JAK) family of tyrosine kinases is associated with various cytokine receptors. JAK1 and JAK3 play particularly important roles in the immune response, and their inhibition is expected to provide targeted immune ..
  38. Almiron Bonnin D, Havrda M, Lee M, Liu H, Zhang Z, Nguyen L, et al. Secretion-mediated STAT3 activation promotes self-renewal of glioma stem-like cells during hypoxia. Oncogene. 2018;37:1107-1118 pubmed publisher
    ..a hypoxia-induced pathway that utilizes the Hypoxia Inducible Factor 1α (HIF-1α) transcription factor and the JAK1/2-STAT3 (Janus Kinase 1/2 - Signal Transducer and Activator of Transcription 3) axis to enhance the self-renewal of ..
  39. Wingelhofer B, Maurer B, Heyes E, Cumaraswamy A, Berger Becvar A, de Araujo E, et al. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia. 2018;32:1135-1146 pubmed publisher
    ..Furthermore, AC-4-130 synergistically increased the cytotoxicity of the JAK1/2 inhibitor Ruxolitinib and the p300/pCAF inhibitor Garcinol...
  40. Tanaka N, Asao H, Ohbo K, Ishii N, Takeshita T, Nakamura M, et al. Physical association of JAK1 and JAK2 tyrosine kinases with the interleukin 2 receptor beta and gamma chains. Proc Natl Acad Sci U S A. 1994;91:7271-5 pubmed
    ..Monoclonal antibodies specific for the beta chain and gamma chain coimmunoprecipitated JAK1 and 114-kDa JAK2 tyrosine kinases, respectively...
  41. Liu B, Chen S, Guan Y, Chen L. Type III Interferon Induces Distinct SOCS1 Expression Pattern that Contributes to Delayed but Prolonged Activation of Jak/STAT Signaling Pathway: Implications for Treatment Non-Response in HCV Patients. PLoS ONE. 2015;10:e0133800 pubmed publisher
    ..More importantly, faster but shorter induction of SOCS1 by IFN-λ may contribute to delayed but prolonged activation of IFN signaling and ISG expression kinetics by type III IFN. ..
  42. Mo X, Zhang H, Preston S, Martin K, Zhou B, Vadalia N, et al. Interferon-γ Signaling in Melanocytes and Melanoma Cells Regulates Expression of CTLA-4. Cancer Res. 2018;78:436-450 pubmed publisher
    ..Mechanistically, IFNG activated CTLA4 expression through JAK1/2-dependent phosphorylation of STAT1, which bound a specific gamma-activated sequence site on the CTLA4 promoter, ..
  43. Lee S, Strunk K, Spritz R. A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes. Oncogene. 1993;8:3403-10 pubmed
    ..We mapped 16 of the corresponding protein tyrosine kinase genes to specific human chromosomes, identifying a total of 19 human genetic loci, some of which may constitute candidate genes for genetic disorders of mammalian development. ..
  44. Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, et al. Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells. Cell Growth Differ. 2002;13:13-8 pubmed
    ..Here we present evidence that TNF-alpha induces the activation of the cytoplasmic Janus tyrosine kinases Jak1 and Tyk2 in both human healthy peripheral and lymphoma B cells...
  45. 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
    ..In this study, 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...
  46. Mitsiades C. Tight Junction Protein 1: New Insights into Proteasome Inhibitor Resistance and Myeloma Pathophysiology. Cancer Cell. 2016;29:611-612 pubmed publisher
    In this issue of Cancer Cell, Zhang et al. report that TJP1 suppresses EGFR/JAK1/STAT3-mediated signaling and increases the proteasome inhibitor sensitivity of myeloma cells by altering the cellular proteasome capacity versus proteasome ..
  47. Chen Y, Xu Y, Zhang H, Yin J, Fan X, Liu D, et al. Emodin alleviates jejunum injury in rats with sepsis by inhibiting inflammation response. Biomed Pharmacother. 2016;84:1001-1007 pubmed publisher
    ..In conclusion, these results indicate that emodin suppresses inflammatory response induced by sepsis. Emodin activates JAK1/STAT3 signaling pathway and regulates Bcl-2 and Bax expression to protect the jejunum in rats with sepsis.
  48. Bajusz D, Ferenczy G, Keserű G. Ensemble docking-based virtual screening yields novel spirocyclic JAK1 inhibitors. J Mol Graph Model. 2016;70:275-283 pubmed publisher
    ..In this study, a large supplier database was screened to identify novel chemistry starting points for JAK1. The docking-based screening was followed up by testing ten hit compounds experimentally, out of which five have ..
  49. Craiglow B, Liu L, King B. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol. 2017;76:29-32 pubmed publisher
    ..Tofacitinib is a promising therapy for AA in adolescents. The use of tofacitinib and other Janus kinase inhibitors for the treatment of AA in this age group should be further evaluated in prospective clinical trials. ..
  50. Smigiel J, Parameswaran N, Jackson M. Potent EMT and CSC Phenotypes Are Induced By Oncostatin-M in Pancreatic Cancer. Mol Cancer Res. 2017;15:478-488 pubmed publisher
    ..Suppression of JAK1/2 by ruxolitinib prevented STAT3-mediated transcription of ZEB1, SNAI1 and OSMR, as well as the ..
  51. Degryse S, Cools J. JAK kinase inhibitors for the treatment of acute lymphoblastic leukemia. J Hematol Oncol. 2015;8:91 pubmed publisher
    ..leukemia have identified activating mutations in components of the interleukin-7 receptor complex (IL7R, JAK1, and JAK3)...
  52. Nash O, Omotuyi O, Lee J, Kwon B, Ogbadu L. Artocarpus altilis CG-901 alters critical nodes in the JH1-kinase domain of Janus kinase 2 affecting upstream JAK/STAT3 signaling. J Mol Model. 2015;21:280 pubmed publisher
    ..In comparison to JAK1 and Apo-state JAK2, JAK2-bound CG-901 exhibited a highly re-organized key intra-domain protein network; indicating ..
  53. Delconte R, Kolesnik T, Dagley L, Rautela J, Shi W, Putz E, et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat Immunol. 2016;17:816-24 pubmed publisher
    ..Correspondingly, CIS interacted with the tyrosine kinase JAK1, inhibiting its enzymatic activity and targeting JAK for proteasomal degradation...
  54. Lawrence D, Kornbluth J. E3 ubiquitin ligase NKLAM ubiquitinates STAT1 and positively regulates STAT1-mediated transcriptional activity. Cell Signal. 2016;28:1833-1841 pubmed publisher
    ..In this report we show that JAK1 and STAT1 in macrophages deficient in an E3 ubiquitin ligase termed Natural Killer Lytic-Associated Molecule (NKLAM)..
  55. Curran S, Shyer J, St Angelo E, Talbot L, Sharma S, Chung D, et al. Human Dendritic Cells Mitigate NK-Cell Dysfunction Mediated by Nonselective JAK1/2 Blockade. Cancer Immunol Res. 2017;5:52-60 pubmed publisher
    ..human dendritic cell (DC) subtypes, we compared the effects of a JAK2-specific (TG101348) with a less selective JAK1/2 (ruxolitinib) inhibitor on NK-cell activation and function...
  56. Sakatsume M, Igarashi K, Winestock K, Garotta G, Larner A, Finbloom D. The Jak kinases differentially associate with the alpha and beta (accessory factor) chains of the interferon gamma receptor to form a functional receptor unit capable of activating STAT transcription factors. J Biol Chem. 1995;270:17528-34 pubmed
    ..chain, we show that these cells did not activate Jak kinases or STAT proteins with human IFN gamma, even though Jak1 co-immunoprecipitated with the alpha chain...
  57. Ren Y, Zhang Y, Liu R, Fenstermacher D, Wright K, Teer J, et al. JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations. Sci Rep. 2013;3:3042 pubmed publisher
    ..We have found 50 JAK1 truncating mutations in 36 of 635 gynecologic tumors in the Total Cancer Care® (TCC®) tumor bank...
  58. Heyne K, Förster J, Schüle R, Roemer K. Transcriptional repressor NIR interacts with the p53-inhibiting ubiquitin ligase MDM2. Nucleic Acids Res. 2014;42:3565-79 pubmed publisher
    ..In sum, our findings suggest that NIR can support MDM2 to suppress p53 as a transcriptional activator. ..
  59. Kim H, Kim M, Choo H, Chong Y. Novel JAK1-selective benzimidazole inhibitors with enhanced membrane permeability. Bioorg Med Chem Lett. 2016;26:3213-3215 pubmed publisher
    The previously identified Janus kinase 1 (JAK1)-selective inhibitor, 1-(2-aminoethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole-5-carboxamide (2), suffered from low cell permeability, which resulted in poor pharmacokinetic properties...
  60. Lu W, Tseng S, Chen S, Tighe S, Zhang Y, Liu X, et al. Senescence Mediated by p16INK4a Impedes Reprogramming of Human Corneal Endothelial Cells into Neural Crest Progenitors. Sci Rep. 2016;6:35166 pubmed publisher
    ..Day 21 to Day 42 by switching EGF-containing SHEM to LIF/bFGF-containing MESCM through transient activation of LIF-JAK1-STAT3 signaling that delays eventual nuclear translocation of p16INK4a...
  61. Wu K, Li L, Thakur C, Lu Y, Zhang X, Yi Z, et al. Proteomic Characterization of the World Trade Center dust-activated mdig and c-myc signaling circuit linked to multiple myeloma. Sci Rep. 2016;6:36305 pubmed publisher
    ..integrative genomics and proteomics approaches, we further demonstrated that mdig directly interacts with c-myc and JAK1 in MM cell lines, which contributes to hyperactivation of the IL-6-JAK-STAT3 signaling important for the ..
  62. Sliwa T, Beham Schmid C, Burgstaller S, Buxhofer Ausch V, Gastl G, Geissler K, et al. Austrian recommendations for the management of primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis: an expert statement. Wien Klin Wochenschr. 2017;129:293-302 pubmed publisher
    ..Additional treatment options are being explored. ..
  63. Chen Y, Liu W, Wang Y, Zhang L, Wei J, Zhang X, et al. Casein Kinase 2 Interacting Protein-1 regulates M1 and M2 inflammatory macrophage polarization. Cell Signal. 2017;33:107-121 pubmed publisher
    ..Furthermore, CKIP-1 inhibits anti-inflammatory gene expression by negatively regulating JAK1-STAT6 activation in macrophages...
  64. Clay T, Russell P, Do H, Sundararajan V, Conron M, Wright G, et al. EGFR and KRAS mutations do not enrich for the activation of IL-6, JAK1 or phosphorylated STAT3 in resected lung adenocarcinoma. Med Oncol. 2017;34:175 pubmed publisher
    ..We undertook a detailed assessment of the IL-6/JAK1/phosphorylated STAT3 (pSTAT3) pathway in resected lung adenocarcinoma specimens, with special interest in whether ..
  65. Guo D, Dunbar J, Yang C, Pfeffer L, Donner D. Induction of Jak/STAT signaling by activation of the type 1 TNF receptor. J Immunol. 1998;160:2742-50 pubmed
    ..that murine TNF induces the tyrosine phosphorylation and activation of the intracellular Janus tyrosine kinases Jak1, Jak2, and Tyk2 in murine 3T3-L1 adipocytes...
  66. Jiang Q, Li W, Aiello F, Mazzucchelli R, Asefa B, Khaled A, et al. Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev. 2005;16:513-33 pubmed
    ..There remain significant questions regarding IL-7 production and the major producing cells have yet to be fully characterized. ..
  67. 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
    ..CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3...
  68. Zhang D, Wlodawer A, Lubkowski J. Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1. J Mol Biol. 2016;428:4651-4668 pubmed publisher
    The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the ..
  69. Domanski P, Yan H, Witte M, Krolewski J, Colamonici O. Homodimerization and intermolecular tyrosine phosphorylation of the Tyk-2 tyrosine kinase. FEBS Lett. 1995;374:317-22 pubmed
    ..The formation of the Tyk-2 homodimer is independent of both tyrosine phosphorylation and the presence of the tyrosine kinase domain. ..
  70. Friedmann M, Migone T, Russell S, Leonard W. Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation. Proc Natl Acad Sci U S A. 1996;93:2077-82 pubmed
    ..In COS-7 cells, overexpression of Jak1 augmented phosphorylation of Y338 as well as Y392 and Y510, suggesting that the role for this Jak kinase may extend ..
  71. Kim C, Baek S, Um J, Shim B, Ahn K. Resveratrol attenuates constitutive STAT3 and STAT5 activation through induction of PTPε and SHP-2 tyrosine phosphatases and potentiates sorafenib-induced apoptosis in renal cell carcinoma. BMC Nephrol. 2016;17:19 pubmed publisher
    ..and STAT5 (tyrosine residue 694 and 699) activation, which correlated with the suppression of the upstream kinases (JAK1, JAK2, and c-Src) in RCC...
  72. Nada H, El Sharkawy D, Elmasry M, Rashed L, Mamdouh S. Expression of Janus Kinase 1 in vitiligo & psoriasis before and after narrow band UVB: a case-control study. Arch Dermatol Res. 2018;310:39-46 pubmed publisher
    ..The aim of this study was to assess the level of JAK1 in both vitiligo and psoriasis patients before and after treatment with NB-UVB which is considered a gold standard ..
  73. Lee W, Liu F, Lin J, Huang S, Lin H, Liao W, et al. JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis. J Cell Biochem. 2009;106:929-36 pubmed publisher
    ..First, we demonstrate that IL-5 induced c-Myc RNA and protein expressions, as well as activated Janus kinases (JAK1 and JAK2) and signal transducer and activator of transcription-5b (STAT5b)...
  74. Silva P, Nelson C, Driver J, Thatcher W, Chebel R. Effect of recombinant bovine somatotropin on leukocyte mRNA expression for genes related to cell energy metabolism, cytokine production, phagocytosis, oxidative burst, and adaptive immunity. J Dairy Sci. 2017;100:8471-8483 pubmed publisher
    ..1 vs. rbST125 = 1.9 ± 0.1 optical density). On d -7 relative to calving, leukocyte mRNA expression of IGF1R and JAK1 tended to be downregulated and expression of DEFB3 tended to be upregulated by rbST treatment...
  75. Porcu M, Gielen O, Cools J, De Keersmaecker K. JAK1 mutation analysis in T-cell acute lymphoblastic leukemia cell lines. Haematologica. 2009;94:435-7 pubmed publisher
  76. Ettersperger J, Montcuquet N, Malamut G, Guegan N, Lopez Lastra S, Gayraud S, et al. Interleukin-15-Dependent T-Cell-like Innate Intraepithelial Lymphocytes Develop in the Intestine and Transform into Lymphomas in Celiac Disease. Immunity. 2016;45:610-625 pubmed publisher
    ..Overall we characterized gut T cell-like innate IELs, deciphered their pathway of differentiation and showed their malignant transformation in celiac disease. ..
  77. Pritchard M, Baker E, Callen D, Sutherland G, Wilks A. Two members of the JAK family of protein tyrosine kinases map to chromosomes 1p31.3 and 9p24. Mamm Genome. 1992;3:36-8 pubmed
    A member of a new class of protein tyrosine kinases, JAK1, has been mapped to 1p31.3 by in situ hybridization and Southern blot analysis of a panel of mouse-human hybrid cell lines...
  78. 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...
  79. Kirito K, Suzuki K, Miyamura K, Takeuchi M, Handa H, Okamoto S, et al. Ruxolitinib is effective and safe in Japanese patients with hydroxyurea-resistant or hydroxyurea-intolerant polycythemia vera with splenomegaly. Int J Hematol. 2018;107:173-184 pubmed publisher
    Ruxolitinib, a potent JAK1/JAK2 inhibitor, was found to be superior to the best available therapy (BAT) in controlling hematocrit, reducing splenomegaly, and improving symptoms in the phase 3 RESPONSE study of patients with polycythemia ..
  80. Benbernou N, Muegge K, Durum S. Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7Ralpha. J Biol Chem. 2000;275:7060-5 pubmed
    Interleukin-7 (IL-7) receptor signaling begins with activation of the Janus tyrosine kinases Jak1 and Jak3, which are associated with the receptor complex...
  81. Springuel L, Losdyck E, Saussoy P, Turcq B, Mahon F, Knoops L, et al. Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases. Cell Mol Life Sci. 2016;73:4739-4748 pubmed
    ..We previously reported that the IL-9-dependent TS1 cell line sequentially acquired activating substitutions in JAK1 and JAK3 upon successive selections for growth factor independent and JAK inhibitor-resistant cells, suggestive of ..
  82. Curto Garcia N, Harrison C. An updated review of the JAK1/2 inhibitor (ruxolitininb) in the Philadelphia-negative myeloproliferative neoplasms. Future Oncol. 2017;: pubmed publisher
    Ruxolitinib (Rux), a JAK1/2 inhibitor, has been approved for patients with myelofibrosis and in polycythemia vera with inadequate response/intolerance to hydroxycarbamide...
  83. Sakamoto K, Wehde B, Yoo K, Kim T, Rajbhandari N, Shin H, et al. Janus Kinase 1 Is Essential for Inflammatory Cytokine Signaling and Mammary Gland Remodeling. Mol Cell Biol. 2016;36:1673-90 pubmed publisher
    ..Using a novel mammary gland-specific JAK1 knockout model, we demonstrate here that this tyrosine kinase is essential for the activation of STAT1, STAT3, and ..
  84. Lucet I, Murphy J. Characterization of Ligand Binding to Pseudokinases Using a Thermal Shift Assay. Methods Mol Biol. 2017;1636:91-104 pubmed publisher
    ..Here, we illustrate the utility of the method with the pseudokinases, ErbB3/HER3, ILK, ROP5Bi, JAK1, JAK2, TYK2, MLKL, STRAD, TRIB1, VRK3, and ROR1...
  85. Sirhan S, Lasho T, Hanson C, Mesa R, Pardanani A, Tefferi A. The presence of JAK2V617F in primary myelofibrosis or its allele burden in polycythemia vera predicts chemosensitivity to hydroxyurea. Am J Hematol. 2008;83:363-5 pubmed publisher
    ..02). The current study suggests that JAK2V617F presence identifies PMF patients who are likely to respond to HU therapy, and information on its allele burden helps in assigning the optimal starting dose in individual patients with PV. ..
  86. Siu T, Brubaker J, Fuller P, Torres L, Zeng H, Close J, et al. The Discovery of 3-((4-Chloro-3-methoxyphenyl)amino)-1-((3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl)-1H-pyrazole-4-carboxamide, a Highly Ligand Efficient and Efficacious JAK1 Selective Inhibitor with Favorable Pharmacokinetic Properties. J Med Chem. 2017;: pubmed publisher
    The discovery of a potent selective low dose JAK1 inhibitor suitable for clinical evaluation is described...
  87. Huang H, Lee Y, Chang T. JAK1 N-terminus binds to conserved Box 1 and Box 2 motifs of cytokine receptor common beta subunit but signal activation requires JAK1 C-terminus. J Cell Biochem. 2006;99:1078-84 pubmed
    ..Binding of IL-3 to IL-3R activates Janus kinases JAK1 and JAK2...
  88. Song B, Zhan H, Bian Q, Gu J. Piperlongumine inhibits gastric cancer cells via suppression of the JAK1,2/STAT3 signaling pathway. Mol Med Rep. 2016;13:4475-80 pubmed publisher
    ..The consumption of long peppers is therefore recommended for the prevention and treatment of GC, and PL may be a promising candidate drug for treating GC. ..
  89. 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
    ..we showed that infection of 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...
  90. Simoncic P, Lee Loy A, Barber D, Tremblay M, McGlade C. The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. Curr Biol. 2002;12:446-53 pubmed
    ..We have identified two members of the Janus family of tyrosine kinases (JAKs), JAK1 and JAK3, as bona fide substrates of TCPTP...
  91. Taler M, Shpungin S, Salem Y, Malovani H, Pasder O, Nir U. Fer is a downstream effector of insulin and mediates the activation of signal transducer and activator of transcription 3 in myogenic cells. Mol Endocrinol. 2003;17:1580-92 pubmed
    ..Although in untreated cells Fer binds Jak1 and its tyrosine phosphorylation level is low, insulin treatment induced the phosphorylation of Fer and its ..
  92. Huang H, Lin Y, Chen C, Chang T. Simultaneous activation of JAK1 and JAK2 confers IL-3 independent growth on Ba/F3 pro-B cells. J Cell Biochem. 2005;96:361-75 pubmed
    b>JAK1 and JAK2 are tyrosine kinases involved in the regulation of cell proliferation, differentiation, and survival. These proteins may play a key role in mediating the effects of the cytokine IL-3 on hematopoietic cells...