Journal ArticleDOI
Mechanisms and consequences of Jak–STAT signaling in the immune system
Reads0
Chats0
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
More filters
Journal ArticleDOI
Mutual Regulation of ncRNAs and Chromatin Remodeling Complexes in Normal and Pathological Conditions
Irina V. Bure,Marina V. Nemtsova +1 more
TL;DR: In this paper , a review of chromatin remodeling complexes and ncRNAs, their mutual regulation, role in cellular processes, and potential clinical application is presented, and several successful strategies have been proposed.
Journal ArticleDOI
Phosphatase Ssu72 Is Essential for Homeostatic Balance Between CD4+ T Cell Lineages
Min-Hee Kim,Chang Won Lee +1 more
TL;DR: In this article , the immunoregulatory mechanism of Ssu72 phosphatase in CD4+ T cell differentiation, activation, and phenotypic function is discussed. But, the mechanism by which Ssu-72 in T cells integrates the pathophysiology of multiple immune-mediated diseases is still poorly elucidated.
Journal ArticleDOI
Unleashing Intrinsic Growth Pathways in Regenerating Peripheral Neurons
T Poitras,Douglas W. Zochodne +1 more
TL;DR: In this paper , a review of the major regenerative signaling cascades that are known to influence adult peripheral axon regeneration is presented, emphasizing several molecular barriers to regrowth that have been studied in our laboratory.
Journal ArticleDOI
Making New Connections-Chromosome Conformation Capture for Identification of Disease-Associated Target Genes.
TL;DR: Chromosome conformation capture addresses the problem of susceptibility loci for complex dermatologic diseases by using the spatial organization of chromatin to identify the genes these loci interact with, often across long distances.
References
More filters
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.