JAK-STAT最新文献

{"title":"STAT2 signaling and dengue virus infection.","authors":"Juliet Morrison,&nbsp;Adolfo García-Sastre","doi":"10.4161/jkst.27715","DOIUrl":"https://doi.org/10.4161/jkst.27715","url":null,"abstract":"<p><p>Dengue virus (DENV) is an important human pathogen whose byzantine relationship with the immune response is poorly understood. DENV causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, diseases for which palliative care is the only treatment. DENV immunopathogenesis studies are complicated by the lack of an immunocompetent small-animal model, and this has hindered anti-DENV drug and vaccine development. This review describes strategies that DENV uses to evade the type I interferon response and focuses on how data gained from the study of DENV NS5-mediated STAT2 degradation may be used to create immunocompetent DENV mouse models and design anti-DENV therapeutics. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"3 1","pages":"e27715"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.27715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32299289","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":"Integrating non-coding RNAs in JAK-STAT regulatory networks.","authors":"Steven Witte,&nbsp;Stefan A Muljo","doi":"10.4161/jkst.28055","DOIUrl":"https://doi.org/10.4161/jkst.28055","url":null,"abstract":"<p><p>Being a well-characterized pathway, JAK-STAT signaling serves as a valuable paradigm for studying the architecture of gene regulatory networks. The discovery of untranslated or non-coding RNAs, namely microRNAs and long non-coding RNAs, provides an opportunity to elucidate their roles in such networks. In principle, these regulatory RNAs can act as downstream effectors of the JAK-STAT pathway and/or affect signaling by regulating the expression of JAK-STAT components. Examples of interactions between signaling pathways and non-coding RNAs have already emerged in basic cell biology and human diseases such as cancer, and can potentially guide the identification of novel biomarkers or drug targets for medicine. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"3 1","pages":"e28055"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.28055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32299290","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":"STAT6 and lung inflammation.","authors":"Hannah H Walford,&nbsp;Taylor A Doherty","doi":"10.4161/jkst.25301","DOIUrl":"https://doi.org/10.4161/jkst.25301","url":null,"abstract":"<p><p>Lung inflammation has many etiologies, including diseases of Th2-type immunity, such as asthma and anti-parasitic responses. Inflammatory diseases of the lung involve complex interactions among structural cells (airway epithelium, smooth muscle, and fibroblasts) and immune cells (B and T cells, macrophages, dendritic cells, and innate lymphoid cells). Signal transducer and activator of transcription 6 (STAT6) has been demonstrated to regulate many pathologic features of lung inflammatory responses in animal models including airway eosinophilia, epithelial mucus production, smooth muscle changes, Th2 cell differentiation, and IgE production from B cells. Cytokines IL-4 and IL-13 that are upstream of STAT6 are found elevated in human asthma and clinical trials are underway to therapeutically target the IL-4/IL-13/STAT6 pathway. Additionally, recent work suggests that STAT6 may also regulate lung anti-viral responses and contribute to pulmonary fibrosis. This review will focus on the role of STAT6 in lung diseases and mechanisms by which STAT6 controls immune and structural lung cell function. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 4","pages":"e25301"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.25301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32022109","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":"STAT5 acetylation: Mechanisms and consequences for immunological control and leukemogenesis.","authors":"Christian Kosan,&nbsp;Torsten Ginter,&nbsp;Thorsten Heinzel,&nbsp;Oliver H Krämer","doi":"10.4161/jkst.26102","DOIUrl":"https://doi.org/10.4161/jkst.26102","url":null,"abstract":"<p><p>The cytokine-inducible transcription factors signal transducer and activator of transcription 5A and 5B (STAT5A and STAT5B) are important for the proper development of multicellular eukaryotes. Disturbed signaling cascades evoking uncontrolled expression of STAT5 target genes are associated with cancer and immunological failure. Here, we summarize how STAT5 acetylation is integrated into posttranslational modification networks within cells. Moreover, we focus on how inhibitors of deacetylases and tyrosine kinases can correct leukemogenic signaling nodes involving STAT5. Such small molecules can be exploited in the fight against neoplastic diseases and immunological disorders. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 4","pages":"e26102"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.26102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32023645","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":"JAK-STAT3 and somatic cell reprogramming.","authors":"Yong Tang,&nbsp;Xiuchun Cindy Tian","doi":"10.4161/jkst.24935","DOIUrl":"https://doi.org/10.4161/jkst.24935","url":null,"abstract":"<p><p>Reprogramming somatic cells to pluripotency, especially by the induced pluripotent stem cell (iPSC) technology, has become widely used today to generate various types of stem cells for research and for regenerative medicine. However the mechanism(s) of reprogramming still need detailed elucidation, including the roles played by the leukemia inhibitory factor (LIF) signaling pathway. LIF is central in maintaining the ground state pluripotency of mouse embryonic stem cells (ESCs) and iPSCs by activating the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway. Characterizing and understanding this pathway holds the key to generate naïve pluripotent human iPSCs which will facilitate the development of patient-specific stem cell therapy. Here we review the historical and recent developments on how LIF signaling pathway regulates ESC pluripotency maintenance and somatic cell reprogramming, with a focus on JAK-STAT3. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 4","pages":"e24935"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.24935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32067673","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":"Signal transducer and activator of transcription-1 localizes to the mitochondria and modulates mitophagy.","authors":"Lauren T Bourke,&nbsp;Richard A Knight,&nbsp;David S Latchman,&nbsp;Anastasis Stephanou,&nbsp;James McCormick","doi":"10.4161/jkst.25666","DOIUrl":"https://doi.org/10.4161/jkst.25666","url":null,"abstract":"<p><p>The signal transducer and activator of transcription (STAT) proteins are latent transcription factors that have been shown to be involved in cell proliferation, development, apoptosis, and autophagy. STAT proteins undergo activation by phosphorylation at tyrosine 701 and serine 727 where they translocate to the nucleus to regulate gene expression. STAT1 has been shown to be involved in promoting apoptotic cell death in response to cardiac ischemia/reperfusion and has recently been shown by our laboratory to be involved in negatively regulating autophagy. These processes are thought to promote cell death and restrict cell survival leading to the generation of an infarct. Here we present data that shows STAT1 localizes to the mitochondria and co-immunoprecipitates with LC3. Furthermore, electron microscopy studies also reveal mitochondria from ex vivo I/R treated hearts of STAT1KO mice contained within a double membrane autophagosome indicating that STAT1 may be involved in negatively regulating mitophagy. This is the first description of STAT1 being localized to the mitochondria and also having a role in mitophagy. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 4","pages":"e25666"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.25666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32067674","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":"Non-genomic STAT5-dependent effects at the endoplasmic reticulum and Golgi apparatus and STAT6-GFP in mitochondria.","authors":"Pravin B Sehgal","doi":"10.4161/jkst.24860","DOIUrl":"https://doi.org/10.4161/jkst.24860","url":null,"abstract":"<p><p>STAT protein species are well-known as transcription factors that regulate nuclear gene expression. Recent novel lines of research suggest new non-genomic functions of STAT5A/B and STAT6. It was discovered in human pulmonary arterial endothelial cells that STAT5A, including STAT5A-GFP, constitutively associated with the Golgi apparatus, and both STAT5A and B with the endoplasmic reticulum. Acute siRNA-mediated knockdown of STAT5A/B led to the rapid development of a dramatic cystic change in the endoplasmic reticulum (ER) characterized by deposition of the ER structural protein reticulon-4 (RTN4; also called Nogo-B) and the ER-resident GTPase atlastin-3 (ATL3) along cyst membranes and cyst-zone boundaries, accompanied by Golgi fragmentation. Functional consequences included reduced anterograde trafficking, an ER stress response (increased GRP78/BiP) and eventual mitochondrial fragmentation. This phenotype was \"non-genomic\" in that it was elicited in enucleated cytoplasts. In cross-immunopanning assays STAT5A and B species associated with ATL3, and the ER-lumen spacer CLIMP63 (also called cytoskeleton-associated protein 4, CKAP4) but not RTN4. From a disease significance perspective we posit that STAT5, which is known to be affected by estradiol-17β and prolactin, represents the gender-sensitive determinant in the pathogenesis of idiopathic pulmonary hypertension (IPAH), a disease which includes ER/Golgi dysfunctions but with a 2- to 4-fold higher prevalence in postpubertal women. A separate line of recent research produced evidence for the association of STAT6-GFP, but not STAT3-GFP, STAT3-DsRed, or STAT3-Flag, with mitochondria in live-cell, immunofluorescence, and immunoelectron microscopy. An N-terminal truncation of STAT6-GFP (1-459), which lacked the SH2 domain and Tyr-phosphorylation site, constitutively associated with mitochondria. Thus, the emergent new of biology STAT proteins includes non-genomic roles-structurally and functionally-in the three closely related membrane organelles consisting of the endoplasmic reticulum, Golgi apparatus, and mitochondria. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 4","pages":"e24860"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.24860","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32069323","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":"Role of STAT3 in regulatory T lymphocyte plasticity during acute graft-vs.-host-disease.","authors":"Masayuki Fujino,&nbsp;Xiao-Kang Li","doi":"10.4161/jkst.24529","DOIUrl":"https://doi.org/10.4161/jkst.24529","url":null,"abstract":"<p><p>Regulatory T (Treg) lymphocytes are important mediators of the allogeneic immune response, although the mechanisms by which they are controlled are not fully understood. Studies conducted in mice, including a recent article in Immunity by Laurence et al., have shown that STAT3 is an important factor involved in the instability of natural Treg (nTreg) lymphocytes and the generation of induced Treg (iTreg) lymphocytes. The authors used T lymphocytes obtained from Foxp3-GFP reporter mice, which allowed them to track the in vivo fate of the nTreg and iTreg lymphocyte populations in the inflammatory milieu of acute GvHD. They showed that nTreg lymphocytes lose the expression of FoxP3 within this inflammatory environment and that the loss of FoxP3 is, in part, STAT3-dependent. Ultimately, the absence of STAT3 permitted the conversion of transferred naive CD4(+) T lymphocytes to iTreg lymphocytes, which correlated with a strikingly improved survival rate during GvHD. We herein discuss how the article by Laurence et al. offers a novel mechanism to explain how the inflammatory environment may alter the stability or phenotype of Treg lymphocytes. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 4","pages":"e24529"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.24529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32093591","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 novel role for STAT5 in DC: Controlling the Th2-response.","authors":"Aurélie Jeanne Tormo,&nbsp;Jean-François Gauchat","doi":"10.4161/jkst.25352","DOIUrl":"https://doi.org/10.4161/jkst.25352","url":null,"abstract":"<p><p>Dendritic cells (DC) play a key role in immunity by recognizing and presenting antigens. Cytokines and cytokine-activated transcription factors are fundamental in the regulation of the DC differentiation and their functions. While the role of STAT3 in DC development is well established, the function of STAT5 in DC has yet to be fully elucidated. A recent study published in Nature Immunology by Bell et al., using the DC-specific deletion of Stat5, demonstrated the importance of STAT5 in the induction of a Th2 response in DC. As the activation of this transcription factor is not required for the induction of a Th1 response, the authors further investigated the role STAT5 in the signaling to thymic stromal lymphopoietin (TSLP), a cytokine known to be important for type 2 inflammatory responses. Their results demonstrate the importance of STAT5 activation during TLSP-induced Th2 responses and suggest that DC are a key TLSP target. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 4","pages":"e25352"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.25352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32093592","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":"JAK2-STAT5B pathway and osteoblast differentiation.","authors":"Pramod Darvin,&nbsp;Youn Hee Joung,&nbsp;Young Mok Yang","doi":"10.4161/jkst.24931","DOIUrl":"https://doi.org/10.4161/jkst.24931","url":null,"abstract":"<p><p>Osteoblast differentiation is a critical step in the maintenance of bone homeostasis. Osteoblast differentiation is generally maintained by growth hormone (GH) and various other endocrine and autocrine/paracrine factors. JAK2-STAT5B pathway is a central axis in the mechanism of GH signaling. Similarly, the autocrine/paracrine signaling factor IGF-1 also mediates its effects through this pathway. Analysis on JAK2-STAT5B pathway showed its importance in the IGF-1/IGF-1R mediated regulation of gene expression and osteoblast differentiation. Persistent activation of STAT5B and inhibition of STAT5B degradation showed increased osteoblastic differentiation and STAT5B/Runx-2 activities. Conditional gene silencing studies showed the importance of the JAK2-STAT5B pathway in stimulation of other transcription factors and expression of various differentiation markers. </p>","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"2 4","pages":"e24931"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/jkst.24931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32067672","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}