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
Targeting STAT3 Signaling Pathway in Colorectal Cancer.
TL;DR: Signal transducer and activator of transcription 3 (STAT3) is a critical transcription factor that has been firmly associated with colorectal cancer initiation and development.
Journal ArticleDOI
Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options
Thomas Bieber,Amy S. Paller,Kenji Kabashima,M Feely,Maria Jose Rueda,Jorge A. Ross Terres,Andreas Wollenberg +6 more
TL;DR: The diverse cellular and molecular mechanisms involved in AD, including the critical role of T‐cell‐driven inflammation, are described, primarily via T helper (Th) 2‐ and Th17‐derived cytokines, many of which are mediated by the Janus kinase (JAK) signaling pathway.
Journal ArticleDOI
STAT signaling in polycystic kidney disease
Sebastian Strubl,Jacob A. Torres,Alison K. Spindt,Hannah Pellegrini,Max C. Liebau,Thomas Weimbs +5 more
TL;DR: The role of signal transducer and activator of transcription (STAT) signaling pathways in various renal cell types in healthy kidneys as compared to polycystic kidneys is focused on and the possibility to target STAT signaling for PKD therapy is considered.
Journal ArticleDOI
Macrophages Infected by a Pathogen and a Non-pathogen Spotted Fever Group Rickettsia Reveal Differential Reprogramming Signatures Early in Infection.
TL;DR: It is demonstrated that infection with R. conorii results in a profound reprogramming of host gene expression profiles, providing new insights into the early molecular processes hijacked by a pathogenic SFG Rickettsia to establish a replicative niche in macrophage-like cells.
Journal ArticleDOI
JAK-STAT-dependent regulation of scavenger receptors in LPS-activated murine macrophages.
Ryota Hashimoto,Ryo Kakigi,Yuki Miyamoto,Kyoko Nakamura,Seigo Itoh,Hiroyuki Daida,Takao Okada,Youichi Katoh +7 more
TL;DR: Results suggest that JAK-STAT inhibition could be useful in atherosclerosis therapy, at least for atherosclerotic plaques exacerbated by LPS.
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.