Genomes and Genes
janus kinase 1
Summary: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.
- Bose P, Verstovsek S. JAK2 inhibitors for myeloproliferative neoplasms: what is next?. Blood. 2017;130:115-125 pubmed publisherSince its approval in 2011, the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its use in patients with hydroxyurea resistant or intolerant polycythemia vera (..
- Benjamini O, Jain P, Estrov Z, Kantarjian H, Verstovsek S. Therapeutic effects of ruxolitinib in patients with myelofibrosis without clinically significant splenomegaly. Blood. 2012;120:2768-9 pubmed
- Oetjen L, Mack M, Feng J, Whelan T, Niu H, Guo C, et al. Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch. Cell. 2017;171:217-228.e13 pubmed publisher..Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior. ..
- de Oliveira M, Fook Alves V, Eugenio A, Fernando R, Sanson L, de Carvalho M, et al. Anti-myeloma effects of ruxolitinib combined with bortezomib and lenalidomide: A rationale for JAK/STAT pathway inhibition in myeloma patients. Cancer Lett. 2017;403:206-215 pubmed publisher..In this scenario, JAK/STAT pathway could pose as a new therapeutic target to be exploited, since it is constitutively active and contributes to survival of MM tumor cells. ..
- Lu Y, Gu Y, Ding X, Wang J, Chen J, Miao C. Intracellular Ca2+ homeostasis and JAK1/STAT3 pathway are involved in the protective effect of propofol on BV2 microglia against hypoxia-induced inflammation and apoptosis. PLoS ONE. 2017;12:e0178098 pubmed publisher..Propofol could protect BV2 microglia from hypoxia-induced inflammation and apoptosis. The potential mechanisms may involve the maintaining of intracellular Ca2+ homeostasis and the activation of JAK1/STAT3 pathway. ..
- 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..Collectively our findings suggest that unripe fruit of Solanum nigrum could possibly be used as a chemosensitizing agent against Adriamycin resistant cancers. ..
- Liu Y, Chen W, Kung W, Huang H. Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC Genomics. 2017;18:112 pubmed publisher..Through analysis of public available plasma small RNA sequencing data, we found the supporting evidence for the plant miRNAs cross kingdom RNAi within human circulating system. ..
- Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen P, Rumi E, et al. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer. 2014;120:513-20 pubmed..Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea. ..
- Hynes J, Wu H, Kempson J, Duan J, Lu Z, Jiang B, et al. Discovery of potent and efficacious pyrrolopyridazines as dual JAK1/3 inhibitors. Bioorg Med Chem Lett. 2017;27:3101-3106 pubmed publisher..X-ray co-crystal structure determination confirmed the presumed inhibitor binding orientation in JAK3. Efforts to reduce hERG channel inhibition will be described. ..
- Wang C, Sun M, Yuan X, Ji L, Jin Y, Cardona C, et al. Enterovirus 71 suppresses interferon responses by blocking Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling through inducing karyopherin-?1 degradation. J Biol Chem. 2017;292:10262-10274 pubmed publisher..Our study demonstrates a novel mechanism by which antiviral signaling is suppressed through degradation of KPNA1 by activated caspase-3 induced in an enteroviral infection. ..
- Wang Y, Han Z, Fan Y, Zhang J, Chen K, Gao L, et al. MicroRNA-9 Inhibits NLRP3 Inflammasome Activation in Human Atherosclerosis Inflammation Cell Models through the JAK1/STAT Signaling Pathway. Cell Physiol Biochem. 2017;41:1555-1571 pubmed publisher..b>Janus kinase 1 (JAK1) and matrix metalloproteinase 13 (MMP-13) were identified as the target genes of miR-9...
- Verstovsek S, Courby S, Griesshammer M, Mesa R, Brachmann C, Kawashima J, et al. A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia. Leuk Res. 2017;60:11-17 pubmed publisher..0%), somnolence (15.4%), nausea (15.4%), and fatigue (15.4%). Three patients experienced serious AEs (7.7%), with 1 considered related to momelotinib (dyspnea). Peripheral neuropathy occurred in 7 (17.9%) patients (4 PV, 3 ET). ..
- 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..K6G warrants further investigation as a novel therapeutic method to enhance the efficacy of IFN-?/?. ..
- McLendon P, Davis G, Gulick J, Singh S, Xu N, Salomonis N, et al. An Unbiased High-Throughput Screen to Identify Novel Effectors That Impact on Cardiomyocyte Aggregate Levels. Circ Res. 2017;121:604-616 pubmed publisher..Subsequent validation of one of these candidates, Jak1 (Janus kinase 1), a tyrosine kinase of the nonreceptor type, confirmed the usefulness of this approach in identifying ..
- Yang H, Guo H, Li X, Lin J, Zhang W, Zhao J, et al. Viral RNA-Unprimed Rig-I Restrains Stat3 Activation in the Modulation of Regulatory T Cell/Th17 Cell Balance. J Immunol. 2017;199:119-128 pubmed publisher..Collectively, these results uncover an independent functional contribution of the apo-Rig-I/Stat3 interaction in the maintenance of Treg/Th17 cell balance. ..
- Sveen A, Johannessen B, Tengs T, Danielsen S, Eilertsen I, Lind G, et al. Multilevel genomics of colorectal cancers with microsatellite instability-clinical impact of JAK1 mutations and consensus molecular subtype 1. Genome Med. 2017;9:46 pubmed publisher..See related research highlight by Samstein and Chan 10.1186/s13073-017-0438-9. ..
- Lundh M, Bugliani M, Dahlby T, Chou D, Wagner B, Ghiasi S, et al. The immunoproteasome is induced by cytokines and regulates apoptosis in human islets. J Endocrinol. 2017;233:369-379 pubmed publisher..We conclude that beta cells upregulate immuno-proteasome expression and activity in response to IFNγ, likely as a protective response to confine inflammatory signaling. ..
- Chen X, Ding H, Li H, Huang H, Li X, Yang Y, et al. Hesperetin derivative-14 alleviates inflammation by activating PPAR-? in mice with CCl4-induced acute liver injury and LPS-treated RAW264.7 cells. Toxicol Lett. 2017;274:51-63 pubmed publisher..Collectively, HD-14 may be utilized as a potential anti-inflammation monomeric compound in the treatment of acute liver injury. ..
- Babon J, Lucet I, Murphy J, Nicola N, Varghese L. The molecular regulation of Janus kinase (JAK) activation. Biochem J. 2014;462:1-13 pubmed publisher..These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and suggest alternative therapeutic strategies to complement existing ATP-competitive kinase inhibitors. ..
- Zhang S, Fukuda S, Lee Y, Hangoc G, Cooper S, Spolski R, et al. Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling. J Exp Med. 2000;192:719-28 pubmed..Thus, Stat5a is essential for at least certain effects of FL. Moreover, our data confirm that Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function. ..
- 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..74). The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed. ..
- Murakami K, Kobayashi Y, Uehara S, Suzuki T, Koide M, Yamashita T, et al. A Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro. PLoS ONE. 2017;12:e0181126 pubmed publisher..Hence, Jak1 and Jak2 represent novel therapeutic targets for osteoporosis as well as inflammatory bone diseases including rheumatoid arthritis. ..
- Bonni A, Sun Y, Nadal Vicens M, Bhatt A, Frank D, Rozovsky I, et al. Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. Science. 1997;278:477-83 pubmed..These findings suggest that cytokine activation of the JAK-STAT signaling pathway may be a mechanism by which cell fate is controlled during mammalian development. ..