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
Integration of JAK/STAT receptor-ligand trafficking, signalling and gene expression in Drosophila melanogaster cells.
Rachel Moore,Katja L. Vogt,Adelina E. Acosta Martin,Patrick Shire,Martin P. Zeidler,Elizabeth Smythe +5 more
TL;DR: Examination of how endocytic processing contributes to signalling by the single cytokine receptor in Drosophila melanogaster cells, Domeless, identifies an evolutionarily conserved di-leucine (di-Leu) motif that is required for Domeless internalisation and suggests a mechanism by which a single ligand can give rise to different signalling outputs.
Journal ArticleDOI
Extracellular Vesicles in Synovial Fluid from Rheumatoid Arthritis Patients Contain miRNAs with Capacity to Modulate Inflammation
Andrew D Foers,Alexandra L. Garnham,Alexandra L. Garnham,Simon M Chatfield,Simon M Chatfield,Simon M Chatfield,Gordon K. Smyth,Gordon K. Smyth,Lesley Cheng,Andrew F. Hill,Ian P. Wicks,Ian P. Wicks,Ian P. Wicks,Ken C Pang +13 more
TL;DR: In this paper, the extracellular vesicles (EVs) are associated with both the propagation and attenuation of joint inflammation and destruction, but the specific EV content responsible for these processes is largely unknown.
Journal ArticleDOI
Signaling pathways in cancer‐associated fibroblasts: recent advances and future perspectives
Zengli Fang,Qingcai Meng,Jin Xu,Wei Wang,Bo Zhang,Jiang-Kun Liu,Chen Liang,Jie Hua,Yingjun Zhao,Xianjun Yu,Si Shi +10 more
TL;DR: A comprehensive understanding of the signaling cascades in CAFs might help us better understand the roles of CAFs and the tumor microenvironment in cancer progression and may facilitate the development of more efficient and safer stroma-targeted cancer therapies as discussed by the authors .
Journal ArticleDOI
Bridging Radiotherapy to Immunotherapy: The IFN-JAK-STAT Axis.
Lewis Z. Shi,James A. Bonner +1 more
TL;DR: In this paper, the authors conducted a systematic literature search on the molecular underpinnings of radiotherapy-induced immunomodulation and IOs, which identified the IFN-JAK-STAT pathway as a major regulator.
Journal ArticleDOI
STAT Family Protein Expression and Phosphorylation State during moDC Development Is Altered by Platinum-Based Chemotherapeutics.
Nienke de Haas,Coco de Koning,Stefania Di Blasio,Georgina Flórez-Grau,I. Jolanda M. de Vries,Stanleyson V. Hato +5 more
TL;DR: A role for platinum-based chemotherapeutics to enhance DC function via inhibition of STAT signaling, thereby potentially enhancing efficacy of DC-based immunotherapies is suggested.
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.