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Janus kinase 1

Janus kinase, Janus Kinase 1, JAK1
Janus kinase 1 (JAK1), is a member of a new class of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain. The second phosphotransferase domain bears all the hallmarks of a protein kinase, although its structure differs significantly from that of the PTK and threonine/serine kinase family members. JAK1 is a large, widely expressed membrane-associated phosphoprotein. JAK1 is involved in the interferon-alpha/beta and -gamma signal transduction pathways. The reciprocal interdependence between JAK1 and TYK2 activities in the interferon-alpha pathway, and between JAK1 and JAK2 in the interferon-gamma pathway, may reflect a requirement for these kinases in the correct assembly of interferon receptor complexes. These kinases couple cytokine ligand binding to tyrosine phosphorylation of various known signaling proteins and of a unique family of transcription factors termed the signal transducers and activators of transcription, or STATs. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: JAK2, STAT3, CAN, V1a, STAT1
Papers using Janus kinase antibodies
High levels of human gamma-globin gene expression in adult mice carrying a transgene of deletion-type hereditary persistence of fetal hemoglobin.
Supplier
Blagosklonny Mikhail, In PLoS ONE, 1996
... Phospho-ERK1/2 (Thr202/Tyr204), total ERK1/2, phospho-JNK (Thr183/Tyr185), total JNK, phospho-STAT5 (Tyr694), phospho-JAK1 (Tyr1022/1023) antibodies were from Cell Signaling Technologies (Beverly, MA) ...
Papers on Janus kinase
Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled Phase 2a study.
New
Griffiths et al., Stevenage, United Kingdom. In Br J Dermatol, Feb 2016
BACKGROUND: GSK2586184 is a selective oral JAK1 inhibitor being evaluated as a treatment for moderate to severe plaque type psoriasis.
Generalization of Rare Variant Association Tests for Longitudinal Family Studies.
New
Chiu et al., Taipei, Taiwan. In Genet Epidemiol, Feb 2016
When the proposed tests were applied to data from the Diabetes Heart Study, we found exome variants of POMGNT1 and JAK1 genes were associated with type 2 diabetes.
A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis.
New
Menter et al., Montréal, Canada. In J Dermatolog Treat, Feb 2016
BACKGROUND: Chronic plaque psoriasis is partially mediated by elevation of proinflammatory cytokines, including several within the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.
IRS2 silencing increases apoptosis and potentiates the effects of ruxolitinib in JAK2V617F-positive myeloproliferative neoplasms.
New
Traina et al., Campinas, Brazil. In Oncotarget, Feb 2016
However, the lack of complete response in most patients treated with the JAK1/2 inhibitor, ruxolitinib, indicates the need for identifying pathways that cooperate with JAK2.
Myelofibrosis-When Do We Select Transplantation or Non-transplantation Therapeutic Options?
Review
New
Gupta et al., Toronto, Canada. In Curr Hematol Malig Rep, Jan 2016
UNASSIGNED: Janus kinase 1/2 (JAK1/2) inhibitor therapy is effective in alleviating myelofibrosis (MF)-related symptoms.
Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed.
New
Impact
Levy et al., Durham, United States. In J Clin Oncol, Jan 2016
Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer.
MicroRNA let-7i regulates dendritic cells maturation targeting interleukin-10 via the Janus kinase 1-signal transducer and activator of transcription 3 signal pathway subsequently induces prolonged cardiac allograft survival in rats.
New
Wu et al., Harbin, China. In J Heart Lung Transplant, Dec 2015
BACKGROUND: In this study, we investig1ated whether microRNA let-7i regulates dendric cell maturation targeting interleukin-10 (IL-10) via the Janus kinase 1-signal transducer and activator of transcription 3 (JAK1-STAT3) signal pathway subsequently prolongs rat cardiac allograft survival.
Future perspectives in target-specific immunotherapies of myasthenia gravis.
Review
New
Dalakas, Philadelphia, United States. In Ther Adv Neurol Disord, Nov 2015
Novel biological agents currently on the market, directed against the following molecular pathways, are relevant and specific therapeutic targets that can be tested in MG: (a) T cell intracellular signaling molecules, such as anti-CD52, anti-interleukin (IL) 2 receptors, anti- costimulatory molecules, and anti-Janus tyrosine kinases (JAK1, JAK3) that block the intracellular cascade associated with T-cell activation; (b) B cells and their trophic factors, directed against key B-cell molecules; (c) complement C3 or C5, intercepting the destructive effect of complement-fixing antibodies; (d) cytokines and cytokine receptors, such as those targeting IL-6 which promotes antibody production and IL-17, or the p40 subunit of IL-12/1L-23 that affect regulatory T cells; and (e) T and B cell transmigration molecules associated with lymphocyte egress from the lymphoid organs.
Guidelines for the management of myeloproliferative neoplasms.
Review
New
Won et al., Seoul, South Korea. In Korean J Intern Med, Nov 2015
The discovery of new genetic aberrations such as Janus kinase 2 (JAK2) have enhanced our understanding of the pathophysiology of MPNs.
Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.
New
Impact
European T-Cell Lymphoma Study Group et al., Torino, Italy. In Cancer Cell, May 2015
We identified activating mutations of JAK1 and/or STAT3 genes in ∼20% of 88 [corrected] ALK(-) ALCLs and demonstrated that 38% of systemic ALK(-) ALCLs displayed double lesions.
Effect of methotrexate on JAK/STAT pathway activation in myeloproliferative neoplasms.
New
Impact
Zeidler et al., Sheffield, United Kingdom. In Lancet, Mar 2015
BACKGROUND: The myeloproliferative neoplasms are a group of haematological malignancies characterised by pathological activation of the JAK/STAT (Janus kinase and signal transducer and activator of transcription) intracellular signalling pathway.
The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling.
Impact
Hoffmeister et al., Boston, United States. In Nat Med, 2015
Endocytic AMR controls TPO expression through Janus kinase 2 (JAK2) and the acute phase response signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro.
The Role of Reactive Oxygen Species in Myelofibrosis and Related Neoplasms.
Review
Hasselbalch et al., Roskilde, Denmark. In Mediators Inflamm, 2014
A combinatorial approach using old agents with anticancer properties together with novel JAK1/2 inhibitors may open a new era for patients with MPNs, the outlook not only being "minimal residual disease" and potential cure but also a marked improvement in inflammation-mediated comorbidities.
Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals.
Review
González et al., Málaga, Spain. In Antioxidants (basel), 2014
UV radiation reduces cellular antioxidant status by generating reactive oxygen species (ROS), and the resultant oxidative stress alters signal transduction pathways such as the mitogen-activated protein kinase (MAPK), the nuclear factor-kappa beta (NF-κB)/p65, the janus kinase (JAK), signal transduction and activation of transcription (STAT) and the nuclear factor erythroid 2-related factor 2 (Nrf2).
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Impact
Clynes et al., New York City, United States. In Nat Med, 2014
Systemically administered pharmacological inhibitors of Janus kinase (JAK) family protein tyrosine kinases, downstream effectors of the IFN-γ and γc cytokine receptors, eliminated the IFN signature and prevented the development of AA, while topical administration promoted hair regrowth and reversed established disease.
Growth hormone synergizes with BMP9 in osteogenic differentiation by activating the JAK/STAT/IGF1 pathway in murine multilineage cells.
GeneRIF
He et al., Chongqing, China. In J Bone Miner Res, 2012
Growth hormone synergizes with BMP9 in osteogenic differentiation by activating the JAK/STAT/IGF1 pathway in murine multilineage cells
Tyrosine kinase pathways modulate tumor susceptibility to natural killer cells.
GeneRIF
Ritz et al., Boston, United States. In J Clin Invest, 2012
Gene silencing of two members of the JAK family, JAK1 and JAK2, increased the susceptibility of a variety of tumor cell types to natural killer-mediated lysis
Upregulated JAG1 enhances cell proliferation in adrenocortical carcinoma.
GeneRIF
Hammer et al., Ann Arbor, United States. In Clin Cancer Res, 2012
Upregulated JAG1 enhances cell proliferation in adrenocortical carcinoma.
STAT6 and JAK1 are essential for IL-4-mediated suppression of prostaglandin production in human follicular dendritic cells: opposing roles of phosphorylated and unphosphorylated STAT6.
GeneRIF
Choe et al., Ch'unch'ŏn, South Korea. In Int Immunopharmacol, 2012
JAK1 and STAT6 may be universal mediators of IL-4 in the suppression of prostaglandin production in human follicular denritic cells.
Interleukin-13-induced activation of signal transducer and activator of transcription 6 is mediated by an activation of Janus kinase 1 in cultured human bronchial smooth muscle cells.
GeneRIF
Misawa et al., Tokyo, Japan. In Pharmacol Rep, 2011
Janus kinase A is involved in the activation of STAT6 induced by IL-13 in bronchial smooth muscle cells.
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