Genomes and Genes
Summary: A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.
- Rothstein B, Joshipura D, Saraiya A, Abdat R, Ashkar H, Turkowski Y, et al. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib. J Am Acad Dermatol. 2017;76:1054-1060.e1 pubmed publisher..Limitations of the study include the small sample size and open-label study design. Topical ruxolitinib 1.5% cream provided significant repigmentation in facial vitiligo and may offer a valuable new treatment for vitiligo. ..
- Kotkowska A, Sewerynek E, DomaÅ„ska D, Pastuszak Lewandoska D, BrzeziaÅ„ska E. Single nucleotide polymorphisms in the STAT3 gene influence AITD susceptibility, thyroid autoantibody levels, and IL6 and IL17 secretion. Cell Mol Biol Lett. 2015;20:88-101 pubmed publisher..Serum level of IL6 positively correlated with TPOAb in the AITD group. Both studied polymorphisms seem to play a significant role in susceptibility to AITD (HT and GD). STAT3 SNPs may influence TAb level in AITD patients. ..
- Pickering A, Lehr M, Miller R. Lifespan of mice and primates correlates with immunoproteasome expression. J Clin Invest. 2015;125:2059-68 pubmed publisher..This work suggests that augmented immunoproteasome function may contribute to lifespan differences in mice and among primate species. ..
- Ho C, Fan C, Yu H, Wu C, Chen K, Liu S, et al. Testosterone suppresses uropathogenic Escherichia coli invasion and colonization within prostate cells and inhibits inflammatory responses through JAK/STAT-1 signaling pathway. PLoS ONE. 2017;12:e0180244 pubmed publisher..Altogether, this study has provided the possibility that using testosterone in the prevention and clinical treatment of prostatitis is a new direction. ..
- Zhai Z, Boquete J, Lemaitre B. A genetic framework controlling the differentiation of intestinal stem cells during regeneration in Drosophila. PLoS Genet. 2017;13:e1006854 pubmed publisher..Thus, our study provides new insights into the complex and sequential events that are required for rapid differentiation following stem cell division during tissue replenishment. ..
- Laidlaw S, Marukian S, Gilmore R, Cashman S, Nechyporuk Zloy V, Rice C, et al. Tumor Necrosis Factor Inhibits Spread of Hepatitis C Virus Among Liver Cells, Independent From Interferons. Gastroenterology. 2017;153:566-578.e5 pubmed publisher..These findings contradict those from other studies, which have reported that TNF blocks signal transduction in response to IFNs. The destructive inflammatory effects of TNF must be considered along with its antiviral effects. ..
- Marotte H, Tsou P, Fedorova T, Pinney A, Lewis B, Koch A. Blocking the janus-activated kinase pathway reduces tumor necrosis factor alpha-induced interleukin-18 bioactivity by caspase-1 inhibition. Arthritis Res Ther. 2014;16:R102 pubmed publisher..These data present a novel role for JAK inhibition in RA patients and emphasize JAK inhibition use as a new therapeutic option in RA management. ..
- Welsch K, Holstein J, Laurence A, Ghoreschi K. Targeting JAK/STAT signalling in inflammatory skin diseases with small molecule inhibitors. Eur J Immunol. 2017;47:1096-1107 pubmed publisher..JAK/STAT inhibitors will presumably find wide application in dermatology, since they can be applied not only systematically but also topically for the treatment of inflammatory skin diseases...
- Flamant M, Rigaill J, Paul S, Roblin X. Advances in the Development of Janus Kinase Inhibitors in Inflammatory Bowel Disease: Future Prospects. Drugs. 2017;77:1057-1068 pubmed publisher..The availability of these drugs could enhance the therapeutic approach to IBD in the coming years, and reinforce the concept of personalized medicine for IBD patients. ..
- Quan Y, Xu H, Han Y, MesplÃ¨de T, Wainberg M. JAK-STAT Signaling Pathways and Inhibitors Affect Reversion of Envelope-Mutated HIV-1. J Virol. 2017;91: pubmed publisher..JAK-STAT signaling pathways are able to play major roles in these processes. This work sheds new light on factors that can govern HIV infection of target cells. ..
- Mease P, Hall S, Fitzgerald O, van der Heijde D, Merola J, Avila Zapata F, et al. Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis. N Engl J Med. 2017;377:1537-1550 pubmed publisher..We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs)...
- He R, Gu X, Lai W, Peng X, Yang G. Transcriptome-microRNA analysis of Sarcoptes scabiei and host immune response. PLoS ONE. 2017;12:e0177733 pubmed publisher..The differential expression analysis indicated that microRNAs of S. scabiei and hosts have major roles in regulating immune interactions between parasites and hosts. ..
- Silver R, Barel A, Lascu E, Ritchie E, Roboz G, Christos P, et al. The effect of initial molecular profile on response to recombinant interferon-? (rIFN?) treatment in early myelofibrosis. Cancer. 2017;123:2680-2687 pubmed publisher..In this phase 2 study, for the first time, the authors correlate response to rIFN? treatment with driver and HMR mutations...
- Liu Y, Gao X, Deeb D, Zhang Y, Shaw J, Gautam S. Anticancer agent pristimerin inhibits IL-2 induced activation of T lymphocytes. J Exp Ther Oncol. 2016;11:181-188 pubmed..These data demonstrated that PM inhibits IL-2 induced T cell activation and generation of LAK cells by disrupting multiple cell signaling pathways induced by IL-2. ..
- Saeed I, McLornan D, Harrison C. Managing side effects of JAK inhibitors for myelofibrosis in clinical practice. Expert Rev Hematol. 2017;10:617-625 pubmed publisher..The side effect profile, in the most, is predictable and manageable with high degrees of clinical surveillance and dose modifications. ..
- Liu Q, Yu S, Li A, Xu H, Han X, Wu K. Targeting interlukin-6 to relieve immunosuppression in tumor microenvironment. Tumour Biol. 2017;39:1010428317712445 pubmed publisher..We also concluded recent clinical studies targeting interlukin-6 as an immune-based therapeutic intervention in patients with cancer. ..
- Wei C, Wu K, Gao Y, Zhang L, Li D, Luo Z. Magnesium Reduces Hepatic Lipid Accumulation in Yellow Catfish (Pelteobagrus fulvidraco) and Modulates Lipogenesis and Lipolysis via PPARA, JAK-STAT, and AMPK Pathways in Hepatocytes. J Nutr. 2017;147:1070-1078 pubmed publisher..PPARA, JAK-STAT, and AMPK pathways mediated the magnesium-induced changes in lipid deposition and metabolism. These results offer new insight into magnesium nutrition in vertebrates. ..
- Gladman D, Rigby W, Azevedo V, Behrens F, Blanco R, Kaszuba A, et al. Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors. N Engl J Med. 2017;377:1525-1536 pubmed publisher..We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors...
- Terriente Félix A, Perez L, Bray S, Nebreda A, Milan M. A Drosophila model of myeloproliferative neoplasm reveals a feed-forward loop in the JAK pathway mediated by p38 MAPK signalling. Dis Model Mech. 2017;10:399-407 pubmed publisher..Based on the shared molecular mechanisms underlying MPNs in flies and humans, the interplay between Drosophila JAK and p38 signalling pathways unravelled in this work might have translational relevance for human MPNs. ..
- Wang C, Ding H, Tang X, Li Z, Gan L. Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway. Cell Physiol Biochem. 2017;43:743-756 pubmed publisher..Our findings suggested that Liuweibuqi capsule might effectively ameliorate the progression of COPD via the JAK/STAT pathway. ..
- Malik A, Pal R, Gupta S. Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion. PLoS ONE. 2017;12:e0178269 pubmed publisher..These results suggest cross-communication between ERK½ and JAK-STAT pathways during EGF-mediated increase in invasion of trophoblast cells; phosphorylation at ser 727 residue of both STAT3 and STAT1 appears to be critical. ..
- Zhang W, Dong R, Diao S, Du J, Fan Z, Wang F. Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells. Stem Cell Res Ther. 2017;8:30 pubmed publisher..We identified that one lncRNA, XR_111050, could be a potential target for bone tissue engineering. ..
- Omori I, Yamaguchi H, Miyake K, Miyake N, Kitano T, Inokuchi K. D816V mutation in the KIT gene activation loop has greater cell-proliferative and anti-apoptotic ability than N822K mutation in core-binding factor acute myeloid leukemia. Exp Hematol. 2017;52:56-64.e4 pubmed publisher..These findings establish that D816V and N822K mutations are situated closely on the KIT receptor activation loop, but D816V has greater cell-proliferative and anti-apoptotic ability than N822K. ..
- Sandborn W, Su C, Sands B, D Haens G, Vermeire S, Schreiber S, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017;376:1723-1736 pubmed publisher..Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.). ..
- Yang Q, Qiu H, Xie H, Qi Y, Cha H, Qu J, et al. A Schistosoma japonicum Infection Promotes the Expansion of Myeloid-Derived Suppressor Cells by Activating the JAK/STAT3 Pathway. J Immunol. 2017;198:4716-4727 pubmed publisher..japonicum infection. ..
- Yamagishi H, Inoue T, Nakajima Y, Maeda J, Tominaga H, Usuda H, et al. Discovery of tricyclic dipyrrolopyridine derivatives as novel JAK inhibitors. Bioorg Med Chem. 2017;25:5311-5326 pubmed publisherb>Janus kinases (JAKs) play a crucial role in cytokine mediated signal transduction. JAK inhibitors have emerged as effective immunomodulative agents for the prevention of transplant rejection...
- Huang L, Ma B, Ma J, Wang F. Fractalkine/CX3CR1 axis modulated the development of pancreatic ductal adenocarcinoma via JAK/STAT signaling pathway. Biochem Biophys Res Commun. 2017;493:1510-1517 pubmed publisher..Our investigation helped understanding the pathogenesis of PDAC occurrence, and demonstrated critical role of FKN/CX3CR1 in PDAC development...
- Li Y, Shan Z, Liu C, Yang D, Wu J, Men C, et al. MicroRNA-294 Promotes Cellular Proliferation and Motility through the PI3K/AKT and JAK/STAT Pathways by Upregulation of NRAS in Bladder Cancer. Biochemistry (Mosc). 2017;82:474-482 pubmed publisher..Moreover, miR-294 suppression could promote the sensitivity of T24 cells to cisplatin. We also found miR-294 could upregulate NRAS and activate the PI3K/AKT and JAK/STAT pathways in T24 cells. ..
- Kong G, Wunderlich M, Yang D, Ranheim E, Young K, Wang J, et al. Combined MEK and JAK inhibition abrogates murine myeloproliferative neoplasm. J Clin Invest. 2014;124:2762-73 pubmed publisher..These results provide a strong rationale for further exploration of combined targeting of MEK/ERK and JAK/STAT in treating patients with JMML and MP-CMML. ..
- Rui X, Pan H, Shao S, Xu X. Anti-tumor and anti-angiogenic effects of Fucoidan on prostate cancer: possible JAK-STAT3 pathway. BMC Complement Altern Med. 2017;17:378 pubmed publisher..All these findings provided novel complementary and alternative strategies to treat prostate cancer. ..
- You Z, Timilshina M, Jeong B, Chang J. BJ-2266 ameliorates experimental autoimmune encephalomyelitis through down-regulation of the JAK/STAT signaling pathway. Eur J Immunol. 2017;47:1488-1500 pubmed publisher..We conclude that BJ-2266 regulates the JAK/STAT pathway in response to cytokine signals and subsequently suppresses the differentiation of Th-cell responses...
- Ng I, Yeap Y, Ong L, Jans D, Bogoyevitch M. Oxidative stress impairs multiple regulatory events to drive persistent cytokine-stimulated STAT3 phosphorylation. Biochim Biophys Acta. 2014;1843:483-94 pubmed
- Barbie T, Alexe G, Aref A, Li S, Zhu Z, Zhang X, et al. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth. J Clin Invest. 2014;124:5411-23 pubmed publisher..Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds. ..
- Zhang X, Jin Q, Jin L. High sugar diet disrupts gut homeostasis though JNK and STAT pathways in Drosophila. Biochem Biophys Res Commun. 2017;487:910-916 pubmed publisher..Moreover, the number of commensal bacteria decreased in the high sugar group. Our data suggests that the high caloric diet disrupts gut homeostasis and highlights Drosophila as an ideal model system to explore gastrointestinal disease. ..
- Tsurumaki H, Katano H, Sato K, Imai R, Niino S, Hirabayashi Y, et al. WP1066, a small molecule inhibitor of the JAK/STAT3 pathway, inhibits ceramide glucosyltransferase activity. Biochem Biophys Res Commun. 2017;491:265-270 pubmed publisher..2 ?M, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C6-NBD-cermide and UDP-glucose. ..
- Zhao G, Liu L, Su B, Zhang T, Chen P, Li W, et al. The dynamic changes of interferon lambdas related genes and proteins in JAK/STAT pathway in both acute and chronic HIV-1 infected patients. AIDS Res Ther. 2017;14:31 pubmed publisher..The dynamic changes of IFNs related genes in JAK-STAT pathway in acute HIV-1 infection will deepen our understanding of the roles of IFN-lambdas in HIV pathogenesis. ..
- Pirault J, Polyzos K, Petri M, Ketelhuth D, Bäck M, Hansson G. The inflammatory cytokine interferon-gamma inhibits sortilin-1 expression in hepatocytes via the JAK/STAT pathway. Eur J Immunol. 2017;47:1918-1924 pubmed publisher..This reduced the expression of sortilin-1, while disrupting the IFN-? signaling pathway prevented the effect. These data unravel an intricate mechanism by which inflammation modulates receptors involved in lipoprotein turnover. ..
- Szydłowski M, Prochorec Sobieszek M, Szumera Ciećkiewicz A, Derezinska E, Hoser G, Wasilewska D, et al. Expression of PIM kinases in Reed-Sternberg cells fosters immune privilege and tumor cell survival in Hodgkin lymphoma. Blood. 2017;130:1418-1429 pubmed publisher..Inhibition of PIM kinases decreases RS cell viability and disrupts signaling circuits that link these cells with their niches. Thus, PIM kinases are promising therapeutic targets in cHL. ..
- Radhakrishnan H, Ilm K, Walther W, Shirasawa S, Sasazuki T, Daniel P, et al. MACC1 regulates Fas mediated apoptosis through STAT1/3 - Mcl-1 signaling in solid cancers. Cancer Lett. 2017;403:231-245 pubmed publisher..Altogether, we reveal a novel death receptor-mediated apoptosis regulatory mechanism by MACC1 in solid cancers through modulation of the STAT1/3-Mcl-1 axis. ..
- Glass C, Wuertzer C, Cui X, Bi Y, Davuluri R, Xiao Y, et al. Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia. PLoS ONE. 2013;8:e67134 pubmed publisher..These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia. ..
- Aguilar Pimentel A, Graessel A, Alessandrini F, Fuchs H, Gailus Durner V, Hrabe de Angelis M, et al. Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma. PLoS ONE. 2017;12:e0178563 pubmed publisher..The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis. ..
- Lui A, Geanes E, Ogony J, Behbod F, Marquess J, Valdez K, et al. IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer inÂ vivo by JAK/STAT-mediated induction of p21. Cancer Lett. 2017;399:29-43 pubmed publisher..These findings suggest IFITM1 overexpression contributes to breast cancer progression and that targeting IFITM1 may be therapeutically beneficial to patients with endocrine-resistant disease. ..
- McGregor G, Irving A, Harvey J. Canonical JAK-STAT signaling is pivotal for long-term depression at adult hippocampal temporoammonic-CA1 synapses. FASEB J. 2017;31:3449-3466 pubmed publisher..McGregor, G., Irving, A. J., Harvey, J. Canonical JAK-STAT signaling is pivotal for long-term depression at adult hippocampal temporoammonic-CA1 synapses. ..
- Gotlib J. Tyrosine Kinase Inhibitors in the Treatment of Eosinophilic Neoplasms and Systemic Mastocytosis. Hematol Oncol Clin North Am. 2017;31:643-661 pubmed publisher..Use of tyrosine kinase inhibitors as a bridge to hematopoietic stem cell transplantation, and development of more selective and potent tyrosine kinase inhibitors is also highlighted. ..
- Su Y, Wang Q, Yang B, Wu L, Cheng G, Kuang H. Withasteroid B from D. metel L. regulates immune responses by modulating the JAK/STAT pathway and the IL-17+ ROR?t+ /IL-10+ FoxP3+ ratio. Clin Exp Immunol. 2017;190:40-53 pubmed publisher..These findings suggest that B2 might mediate the therapeutic effects observed in psoriasis patients following treatment with D. metel L. ..
- Kuuliala K, Kuuliala A, Koivuniemi R, Kautiainen H, Repo H, Leirisalo Repo M. Baseline JAK phosphorylation profile of peripheral blood leukocytes, studied by whole blood phosphospecific flow cytometry, is associated with 1-year treatment response in early rheumatoid arthritis. Arthritis Res Ther. 2017;19:75 pubmed publisher..This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA...
- Lee S, Kang S, Choi M, Jung S, Ryu M, Chung H, et al. Growth Differentiation Factor 15 Mediates Systemic Glucose Regulatory Action of T-Helper Type 2 Cytokines. Diabetes. 2017;66:2774-2788 pubmed publisher..Thus, beneficial effects of Th2 cytokines on systemic glucose metabolism and insulin sensitivity are mediated by GDF15. These findings open up a potential pharmacological route for reversing insulin resistance associated with obesity. ..