Journal ArticleDOI
Mechanisms and consequences of Jak–STAT signaling in the immune system
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TLDR
Recent advances in Jak–STAT biology are reviewed, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.Abstract:
Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced breakneck growth in the quarter century since its discovery and has yielded a stream of basic and clinical insights that have profoundly influenced modern understanding of human health and disease, exemplified by the bench-to-bedside success of Jak inhibitors ('jakinibs') and pathway-targeting drugs. Here we review recent advances in Jak-STAT biology, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.read more
Citations
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Efficacy of WWQ-131, a highly selective JAK2 inhibitor, in mouse models of myeloproliferative neoplasms.
Huan Ge,Caolin Wang,Chao Tian,Yanyan Diao,Wan-Qiao Wang,Xiangyu Ma,Jian Zhang,Honglin Li,Zhenjiang Zhao,Lili Zhu +9 more
TL;DR: In this paper , the authors showed that WWQ-131 was a highly selective JAK2 inhibitor (IC50 = 2.36 nM), with 182-fold and 171-fold more selective to JAK1 and JAK3, respectively.
Journal ArticleDOI
Emerging Role of Plant-Based Dietary Components in Post-Translational Modifications Associated with Colorectal Cancer
TL;DR: In this paper , a review aimed to collect the main PTMs associated with colorectal cancer, analyse the relationship between different proteins that are susceptible to inappropriate PTMs, and review the available scientific literature on the role of plant-based dietary compounds in modulating CRC-associated PTMs.
Peer Review
Drug’s repurposing for Covid-19: A comprehensive Review
TL;DR: The current understanding of the features of SARS ‐ CoV ‐ 2 and the pathophysiological mechanisms, and treatments of various drugs which are repurpose in COVID ‐ 19 are reviewed.
Journal ArticleDOI
Network pharmacology-based approach to explore the underlying mechanism of sinomenine on sepsis-induced myocardial injury in rats
TL;DR: In this article , the authors investigated the role of sinomenine (SIN) on sepsis-induced myocardial injury (MI) and clarified the underlying mechanism based on the techniques of network pharmacology.
Journal ArticleDOI
Topical and systemic JAK inhibitors in hand eczema – a narrative review
TL;DR: In this paper , a review of available data concerning JAK inhibitors' use in hand eczema patients, regarding also clinical trials for the HE treatment is provided, where the authors highlight the potential risks and benefits resulting from the treatment, as well as impact of the therapy on patients' QoL.
References
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Journal ArticleDOI
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
TL;DR: The authors showed that CD4+CD25+ cells contribute to maintaining self-tolerance by downregulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage.
Journal ArticleDOI
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Journal ArticleDOI
A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Robert Kralovics,Francesco Passamonti,Andreas Buser,Soon Siong Teo,Ralph Tiedt,Jakob Passweg,André Tichelli,Mario Cazzola,Radek C. Skoda +8 more
TL;DR: Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
Journal ArticleDOI
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.
E. Joanna Baxter,Linda M. Scott,Peter J. Campbell,Clare L. East,Nasios Fourouclas,Soheila Swanton,George S. Vassiliou,Anthony J. Bench,Elaine M. Boyd,Natasha Curtin,Michael A. Scott,Wendy N. Erber,Anthony R. Green,Anthony R. Green +13 more
TL;DR: A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders.
Journal ArticleDOI
A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
Chloé James,Valérie Ugo,Jean-Pierre Le Couedic,Judith Staerk,François Delhommeau,Catherine Lacout,Loïc Garçon,Hana Raslova,Roland Berger,Annelise Bennaceur-Griscelli,Jean-Luc Villeval,Stefan N. Constantinescu,Nicole Casadevall,William Vainchenker +13 more
TL;DR: A clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and induces erythrocytosis in a mouse model.