JAK-STAT最新文献

{"title":"STAT signaling in inflammation.","authors":"Mark H Kaplan","doi":"10.4161/jkst.24198","DOIUrl":"https://doi.org/10.4161/jkst.24198","url":null,"abstract":"Since their discovery, STAT proteins have been intimately tied to controlling the development of hematopoietic cells that regulate inflammation, and mediating the responses of target cells to inflammatory cytokines. Although our understanding of STAT protein-dependent gene expression during inflammation has grown considerably over the past 15 years, the identification of new cell types that require STAT proteins for development, and new gene targets of STAT-dependent regulation, has added to the already complex network of cells and cytokines in immune-mediated diseases. The review articles in this special focus provide perspective on a number of areas of recent research and highlight some of the next important questions in understanding how STAT proteins contribute to inflammatory disease.","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e24198"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.24198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of the JAK-STAT pathway.","authors":"Clifford Liongue,&nbsp;Alister C Ward","doi":"10.4161/jkst.22756","DOIUrl":"https://doi.org/10.4161/jkst.22756","url":null,"abstract":"<p><p>The JAK-STAT pathway represents a finely tuned orchestra capable of rapidly facilitating an exquisite symphony of responses from a complex array of extracellular signals. This review explores the evolution of the JAK-STAT pathway: the origins of the individual domains from which it is constructed, the formation of individual components from these basic building blocks, the assembly of the components into a functional pathway, and the subsequent reiteration of this basic template to fulfill a variety of roles downstream of cytokine receptors. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e22756"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.22756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT3 activation: A key factor in tumor immunoescape.","authors":"Cédric Rébé,&nbsp;Frédérique Végran,&nbsp;Hélène Berger,&nbsp;François Ghiringhelli","doi":"10.4161/jkst.23010","DOIUrl":"https://doi.org/10.4161/jkst.23010","url":null,"abstract":"<p><p>Cancer growth is controlled by cancer cells (cell intrinsic phenomenon), but also by the immune cells in the tumor microenvironment (cell extrinsic phenomenon). Thus cancer progression is mediated by the activation of transcription programs responsible for cancer cell proliferation, but also induced proliferation/activation of immunosuppressive cells such as Th17, Treg or myeloid derived suppressor cells (MDSCs). One of the key transcription factors involved in these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on STAT3 activation in immune cells, and how it impacts on tumor progression. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e23010"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.23010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rapid conformational rearrangement of STAT1 dimers is required for termination rather than for amplification of interferon-γ signaling.","authors":"Julia Staab,&nbsp;Christoph Herrmann-Lingen,&nbsp;Thomas Meyer","doi":"10.4161/jkst.23576","DOIUrl":"https://doi.org/10.4161/jkst.23576","url":null,"abstract":"<p><p>Sequence-specific binding of STAT1 (signal transducer and activator of transcription 1) transcription factor to palindromic promoter elements, termed γ-activated sites (GAS), and an extended spatial reorientation between two dimer configurations are key events in the interferon signaling pathway. Although the DNA-binding domain of STAT1 is engaged in both processes, how the conformational change from a parallel to an antiparallel dimer configuration affects cytokine-induced target gene activation is unknown. In order to study the impact of the conformational shift on gene expression, we generated a STAT1 point mutant with a structurally altered architecture of the DNA-binding domain and characterized the resulting mutant (F364A) in cells stimulated with interferon-γ. Here, we report that substituting alanine for phenylalanine at position 364 resulted in reduced affinity to GAS sites and, additionally, a decreased dephosphorylation rate by the inactivating Tc45 phosphatase. The mutant had no defect in cooperative DNA binding and displayed normal kinetics of interferon-γ-induced nuclear accumulation, despite its elevated level of tyrosine phosphorylation. By assessing the transcriptional activity of the mutant, we found a strikingly robust expression of known interferon-γ-driven target genes, indicating that an impaired stability of the antiparallel dimer configuration can compensate for a reduced affinity to GAS sites. However, the mutant followed changes in ligand-induced receptor activation more slowly than the wild-type molecule, as demonstrated by its elevated phospho-STAT1 concentration following addition of the kinase inhibitor staurosporine to interferon-pretreated cells. This finding showed that the DNA-binding mutant F364A had partially lost its ability to terminate signal transmission rapidly. Thus, the coupling of high-affinity GAS binding to a rapid exchange from a parallel to an antiparallel dimer conformation is not necessarily required for optimal signal amplification, but rather allows for a dynamic signal response and ensures high adaptability to changes in signal input. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e23576"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.23576","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT heterodimers in immunity: A mixed message or a unique signal?","authors":"Greg M Delgoffe,&nbsp;Dario A A Vignali","doi":"10.4161/jkst.23060","DOIUrl":"https://doi.org/10.4161/jkst.23060","url":null,"abstract":"<p><p>Cytokine signals are essential for generating a robust and specialized immune response. These signals are typically transmitted via canonical STAT homodimers. However, the number of STAT molecules utilized by cytokine signaling cascades within immune cells are limited, and so the mechanism used to deliver complex signals remains elusive. Heterodimerization of STAT proteins is one potential mechanism for signals to be modified downstream of the receptor and may play an important role in dictating the targets of specific cytokine signaling. In this review, we discuss our current understanding of the prevalence of STAT heterodimers, how they are formed and what their physiologic role may be in vivo. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e23060"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.23060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine signaling in the differentiation of innate effector cells.","authors":"Hua Huang,&nbsp;Yapeng Li,&nbsp;Xiaopeng Qi","doi":"10.4161/jkst.23531","DOIUrl":"https://doi.org/10.4161/jkst.23531","url":null,"abstract":"<p><p>Innate effector cells, including innate effector cells of myeloid and lymphoid lineages, are crucial components of various types of immune responses. Bone marrow progenitors differentiate into many subsets of innate effector cells after receiving instructional signals often provided by cytokines. Signal transducer and activator of transcription (STATs) have been shown to be essential in the differentiation of various types of innate effector cells. In this review, we focus specifically on the differentiation of innate effector cells, particularly the role of cytokine signaling in the differentiation of innate effector cells. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e23531"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.23531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic targeting of STAT pathways in CNS autoimmune diseases.","authors":"Charles E Egwuagu,&nbsp;Joseph Larkin Iii","doi":"10.4161/jkst.24134","DOIUrl":"https://doi.org/10.4161/jkst.24134","url":null,"abstract":"<p><p>Signal transducers and activators of transcription (STATs) transduce extracellular signals that regulate the initiation, duration and intensity of immune responses. However, unbridled activation of STATs by pro-inflammatory cytokines or growth factors contributes to pathogenic autoimmunity. In this review, we briefly discuss STAT pathways that promote the development and expansion of T cells that mediate two CNS inflammatory diseases, multiple sclerosis (MS) and uveitis. Particular focus is on animal models of MS and uveitis and new approaches to the treatment of CNS autoimmune diseases based on therapeutic targeting of Th17 cells and STAT pathways. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e24134"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.24134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-2 and STAT5 in regulatory T cell development and function.","authors":"Shawn A Mahmud,&nbsp;Luke S Manlove,&nbsp;Michael A Farrar","doi":"10.4161/jkst.23154","DOIUrl":"https://doi.org/10.4161/jkst.23154","url":null,"abstract":"<p><p>Interleukin-2 and its downstream target STAT5 have effects on many aspects of immune function. This has been perhaps best documented in regulatory T cells. In this review we summarize the initial findings supporting a role for IL2 and STAT5 in regulatory T cell development and outline more recent studies describing how this critical signaling pathway entrains regulatory T cell differentiation and affects regulatory T cell function. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e23154"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.23154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT2: A shape-shifting anti-viral super STAT.","authors":"Fatema Z Chowdhury,&nbsp;J David Farrar","doi":"10.4161/jkst.23633","DOIUrl":"https://doi.org/10.4161/jkst.23633","url":null,"abstract":"<p><p>STAT2 is unique among the STAT family of transcription factors in that its activation is driven predominantly by only two classes of cell surface receptors: Type I and III interferon receptors. As such, STAT2 plays a critical role in host defenses against viral infections. Viruses have evolved to target STAT2 by either inhibiting its expression, blocking its activity, or by targeting it for degradation. Consequently, these viral onslaughts have driven remarkable divergence in the STAT2 gene across species that is not observed in other STAT family members. Thus, the evolution of STAT2 may preserve its activity and protect each species in the face of an ever-changing viral community. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e23633"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.23633","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulation of inflammation by interferons and their STATs.","authors":"Isabella Rauch, Mathias Müller, Thomas Decker","doi":"10.4161/jkst.23820","DOIUrl":"10.4161/jkst.23820","url":null,"abstract":"<p><p>Interferons (IFN) are subdivided into type I IFN (IFN-I, here synonymous with IFN-α/β), type II (IFN-γ) and type III IFN (IFN-III/IFN-λ) that reprogram nuclear gene expression through STATs 1 and 2 by forming STAT1 dimers (mainly IFN-γ) or the ISGF3 complex, a STAT1-STAT2-IRF9 heterotrimer (IFN-I and IFN-III). Dominant IFN activities in the immune system are to protect cells from viral replication and to activate macrophages for enhanced effector function. However, the impact of IFN and their STATs on the immune system stretches far beyond these activities and includes the control of inflammation. The goal of this review is to give an overview of the different facets of the inflammatory process that show regulatory input by IFN/STAT. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 1","pages":"e23820"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/55/jkst-2-e23820.PMC3670275.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}