JAK-STAT Pub Date : 2016-11-14 DOI: 10.1080/21623996.2016.1248011

S. Langabeer

引用次数: 16

Constitutive IFNα/β signaling maintains expression of signaling intermediaries for efficient cytokine responses. 组成型IFNα/β信号传导维持有效细胞因子反应的信号中介的表达。

JAK-STAT Pub Date : 2016-05-18 eCollection Date: 2016-01-01 DOI: 10.1080/21623996.2016.1173804

Nicole L Messina, Christopher J P Clarke, Ricky W Johnstone

{"title":"Constitutive IFNα/β signaling maintains expression of signaling intermediaries for efficient cytokine responses.","authors":"Nicole L Messina, Christopher J P Clarke, Ricky W Johnstone","doi":"10.1080/21623996.2016.1173804","DOIUrl":"https://doi.org/10.1080/21623996.2016.1173804","url":null,"abstract":"Interferons (IFNs) are a family of immunoregulatory cytokines with important roles in anti-viral and anti-tumor responses. Type I and II IFNs bind distinct receptors and are associated with different stages of the immune response. There is however, considerable crosstalk between these two cytokines with enhancement of IFNγ responses following IFNα/β priming and loss of IFNα/β receptor (IFNAR) resulting in diminished IFNγ responses. In this study, we sought to define the mechanism of crosstalk between the type I and II IFNs. Our previous reports demonstrated reduced expression of the canonically activated transcription factor signal transducer and activator of transcription (STAT)1, in cells lacking the IFNAR α chain (IFNAR1). Therefore, we used microarray analysis to determine whether reconstitution of STAT1 in IFNAR1-deficient cells was sufficient to restore IFNγ responses. We identified several biological pathways, including the MHC class I antigen presentation pathway, in which STAT1 reconstitution was able to significantly rescue IFNγ-mediated gene regulation in Ifnar1 (-/-) cells. Notably, we also found that in addition to low basal expression of STAT1, cells lacking the IFNAR1 also had aberrant expression of multiple other transcription factors and signaling intermediaries. The studies described herein demonstrate that basal and regulated expression of signaling intermediaries is a mechanism for crosstalk between cytokines including type I and II IFNs. ","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"5 1","pages":"e1173804"},"PeriodicalIF":0.0,"publicationDate":"2016-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21623996.2016.1173804","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34653367","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}

引用次数: 2

IL-6/STAT3 signaling in mice with dysfunctional type-2 ryanodine receptor. 2型ryanodine受体功能障碍小鼠的IL-6/STAT3信号转导

JAK-STAT Pub Date : 2016-03-07 eCollection Date: 2015-01-01 DOI: 10.1080/21623996.2016.1158379

Tai-Qin Huang, Monte S Willis, Gerhard Meissner

{"title":"IL-6/STAT3 signaling in mice with dysfunctional type-2 ryanodine receptor.","authors":"Tai-Qin Huang, Monte S Willis, Gerhard Meissner","doi":"10.1080/21623996.2016.1158379","DOIUrl":"https://doi.org/10.1080/21623996.2016.1158379","url":null,"abstract":"Mice with genetically modified cardiac ryanodine receptor (Ryr2 (ADA/ADA) mice) are impaired in regulation by calmodulin, develop severe cardiac hypertrophy and die about 2 weeks after birth. We hypothesized that the interleukin 6 (IL-6)/signal transducer and activator of transcription-3 (STAT3) signaling pathway has a role in the development of the Ryr2 (ADA/ADA) cardiac hypertrophy phenotype, and determined cardiac function and protein levels of IL-6, phosphorylation levels of STAT3, and downstream targets c-Fos and c-Myc in wild-type and RyR2 (ADA/ADA) mice, mice with a disrupted IL-6 gene, and mice treated with STAT3 inhibitor NSC74859. IL-6 protein levels were increased at postnatal day 1 but not day 10, whereas pSTAT3-Tyr705/STAT3 ratio and c-Fos and c-Myc protein levels increased in hearts of 10-day but not 1-day old Ryr2 (ADA/ADA) mice compared with wild type. Both STAT3 and pSTAT3-Tyr705 accumulated in the nuclear fraction of 10-day old Ryr2 (ADA/ADA) mice compared with wild type. Ryr2 (ADA /ADA) /IL-6(-/-) mice lived 1.5 times longer, had decreased heart to body weight ratio, and reduced c-Fos and c-Myc protein levels. The STAT3 inhibitor NSC74859 prolonged life span by 1.3-fold, decreased heart to body weight ratio, increased cardiac performance, and decreased pSTAT-Tyr705/STAT3 ratio and IL-6, c-Fos and c-Myc protein levels of Ryr2 (ADA /ADA) mice. The results suggest that upregulation of IL-6 and STAT3 signaling contributes to cardiac hypertrophy and early death of mice with a dysfunctional ryanodine receptor. They further suggest that STAT3 inhibitors may be clinically useful agents in patients with altered Ca(2+) handling in the heart. ","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"4 4","pages":"e1158379"},"PeriodicalIF":0.0,"publicationDate":"2016-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21623996.2016.1158379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34511963","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}

引用次数: 3

STAT5a/b contribute to sex bias in vascular disease: A neuroendocrine perspective. STAT5a/b与血管疾病的性别偏见有关:神经内分泌的观点

JAK-STAT Pub Date : 2015-09-18 eCollection Date: 2015-01-01 DOI: 10.1080/21623996.2015.1090658

Pravin B Sehgal, Yang-Ming Yang, Huijuan Yuan, Edmund J Miller

{"title":"STAT5a/b contribute to sex bias in vascular disease: A neuroendocrine perspective.","authors":"Pravin B Sehgal, Yang-Ming Yang, Huijuan Yuan, Edmund J Miller","doi":"10.1080/21623996.2015.1090658","DOIUrl":"https://doi.org/10.1080/21623996.2015.1090658","url":null,"abstract":"Previous studies have elucidated a neuroendocrine mechanism consisting of the hypothalamus (growth hormone releasing hormone, GHRH) - pituitary (growth hormone, GH) - STAT5a/b axis that underlies sex-biased gene expression in the liver. It is now established that male vs female patterned secretion of GHRH, and thus of circulating GH levels (\"pulsatile\" vs \"more continuous\" respectively), leading to differently patterned activation of PY-STAT5a/b in hepatocytes results in sex-biased gene expression of cohorts of hundreds of downstream genes. This review outlines new data in support of a STAT5a/b-based mechanism of sex bias in the vascular disease pulmonary hypertension (PH). Puzzling observations in PH include its 2-4-fold higher prevalence in women but a male-dominance in many rodent models, and, paradoxically, inhibition of PH development by estrogens in such models. We observed that conditional deletion of STAT5a/b in vascular smooth muscle cells (SMC) in mice converted the male-dominant model of chronic hypoxia-induced PH into a female-dominant phenotype. In human idiopathic PH, there was reduced STAT5a/b and PY-STAT5 in cells in late-stage obliterative pulmonary arterial lesions in both men and women. A juxtaposition of the prior liver data with the newer PH-related data drew attention to the hypothalamus-GH-STAT5 axis, which is the major target of estrogens at the level of the hypothalamus. This hypothesis explains many of the puzzling aspects of sex bias in PH in humans and rodent models. The extension of STAT5-anchored mechanisms of sex bias to vascular disease emphasizes the contribution of central neuroendocrine processes in generating sexual dimorphism in different tissues and cell types. ","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"4 3","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2015-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21623996.2015.1090658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34450125","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}

引用次数: 7

LIF signal in mouse embryonic stem cells. 小鼠胚胎干细胞中的LIF信号。

JAK-STAT Pub Date : 2015-09-11 eCollection Date: 2015-01-01 DOI: 10.1080/21623996.2015.1086520

Satoshi Ohtsuka, Yoko Nakai-Futatsugi, Hitoshi Niwa

引用次数: 51

Mitochondrial STAT3 and reactive oxygen species: A fulcrum of adipogenesis? 线粒体STAT3和活性氧:脂肪形成的一个支点?

JAK-STAT Pub Date : 2015-09-11 eCollection Date: 2015-01-01 DOI: 10.1080/21623996.2015.1084084

Adam H Kramer, Rose Kadye, Pascalene S Houseman, Earl Prinsloo

引用次数: 11

Lentiginoses in polycythemia vera patient: Is there a role for JAK2 (V617F) mutation? 真性红细胞增多症患者的扁豆蛋白酶:是否与JAK2 (V617F)突变有关?

JAK-STAT Pub Date : 2015-07-24 eCollection Date: 2015-01-01 DOI: 10.1080/21623996.2015.1071000

Tugba Kevser Uzuncakmak, Sarenur Yilmaz, Ayse Serap Karadag, Necmettin Akdeniz, Ibrahim Akalin

引用次数: 0

The oncogenic FIP1L1-PDGFRα fusion protein displays skewed signaling properties compared to its wild-type PDGFRα counterpart. 致癌FIP1L1-PDGFRα融合蛋白与其野生型PDGFRα对偶物相比，显示出扭曲的信号特性。

JAK-STAT Pub Date : 2015-07-17 eCollection Date: 2015-01-01 DOI: 10.1080/21623996.2015.1062596

Serge Haan, Christelle Bahlawane, Jiali Wang, Petr V Nazarov, Arnaud Muller, René Eulenfeld, Claude Haan, Catherine Rolvering, Laurent Vallar, Venkata P Satagopam, Thomas Sauter, Monique Yvonne Wiesinger

{"title":"The oncogenic FIP1L1-PDGFRα fusion protein displays skewed signaling properties compared to its wild-type PDGFRα counterpart.","authors":"Serge Haan, Christelle Bahlawane, Jiali Wang, Petr V Nazarov, Arnaud Muller, René Eulenfeld, Claude Haan, Catherine Rolvering, Laurent Vallar, Venkata P Satagopam, Thomas Sauter, Monique Yvonne Wiesinger","doi":"10.1080/21623996.2015.1062596","DOIUrl":"https://doi.org/10.1080/21623996.2015.1062596","url":null,"abstract":"Aberrant activation of oncogenic kinases is frequently observed in human cancers, but the underlying mechanism and resulting effects on global signaling are incompletely understood. Here, we demonstrate that the oncogenic FIP1L1-PDGFRα kinase exhibits a significantly different signaling pattern compared to its PDGFRα wild type counterpart. Interestingly, the activation of primarily membrane-based signal transduction processes (such as PI3-kinase- and MAP-kinase- pathways) is remarkably shifted toward a prominent activation of STAT factors. This diverging signaling pattern compared to classical PDGF-receptor signaling is partially coupled to the aberrant cytoplasmic localization of the oncogene, since membrane targeting of FIP1L1-PDGFRα restores activation of MAPK- and PI3K-pathways. In stark contrast to the classical cytokine-induced STAT activation process, STAT activation by FIP1L1-PDGFRα does neither require Janus kinase activity nor Src kinase activity. Furthermore, we investigated the mechanism of STAT5 activation via FIP1L1-PDGFRα in more detail and found that STAT5 activation does not involve an SH2-domain-mediated binding mechanism. We thus demonstrate that STAT5 activation occurs via a non-canonical activation mechanism in which STAT5 may be subject to a direct phosphorylation by FIP1L1-PDGFRα. ","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"4 1","pages":"e1062596"},"PeriodicalIF":0.0,"publicationDate":"2015-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21623996.2015.1062596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34210322","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}

引用次数: 5

Loss of WAVE3 sensitizes triple-negative breast cancers to chemotherapeutics by inhibiting the STAT-HIF-1α-mediated angiogenesis. WAVE3的缺失通过抑制stat - hif -1α-介导的血管生成使三阴性乳腺癌对化疗药物敏感。

JAK-STAT Pub Date : 2015-02-03 eCollection Date: 2014-01-01 DOI: 10.1080/21623996.2015.1009276

Gangarao Davuluri, William P Schiemann, Edward F Plow, Khalid Sossey-Alaoui

{"title":"Loss of WAVE3 sensitizes triple-negative breast cancers to chemotherapeutics by inhibiting the STAT-HIF-1α-mediated angiogenesis.","authors":"Gangarao Davuluri, William P Schiemann, Edward F Plow, Khalid Sossey-Alaoui","doi":"10.1080/21623996.2015.1009276","DOIUrl":"https://doi.org/10.1080/21623996.2015.1009276","url":null,"abstract":"Chemoresistance allows for disease to recur and ultimately causes the death of most breast cancer patients. This scenario is particularly relevant in patients harboring triple-negative breast cancer (TNBC) tumors for which there are no effective FDA-approved drugs. However, a recent study determined that TNBCs can be segregated into 6 genetically distinct subtypes that do in fact exhibit differential rates of pathological complete response (pCR) to standard-of-care chemotherapies. Of these, the mesenchymal and mesenchymal stem-like subtypes of TNBCs exhibit the lowest rates of pCR when treated with standard-of-care chemotherapies. WAVE3 is an actin-cytoskeleton remodeling protein, and recent studies have highlighted a potential role for WAVE3 in promoting tumor progression and metastasis in TNBC. However, whether WAVE3 activity is involved in the development of chemoresistance in TNBCs remains unclear. Here we show that loss of WAVE3 expression resensitizes human TNBC cells to doxorubicin and docetaxel, as measured by increased apoptosis and cell death. We also show that WAVE3 knockdown in the chemotherapy-treated TNBC cells results in inhibition of STAT1 phosphorylation, as well as a significant decrease in expression levels of its downstream effector HIF-1α. Since HIF-1α is a major activator of VEGF-A production, and therefore a stimulator of tumor angiogenesis, loss of HIF-1α in the WAVE3-knockdown cells resulted in the inhibition the chemotherapy-mediated VEGF-A secretion and the downstream activation of angiogenesis, a phenomenon that often accompanies chemoresistance. Our data identify a critical role of WAVE3 in sensitizing TNBC to chemotherapy by inhibiting the STAT1→HIF-1α→VEGF-A signaling axis, and support the possibility that WAVE3 inhibition may be a promising target for TNBC cancer therapy. ","PeriodicalId":89791,"journal":{"name":"JAK-STAT","volume":"3 4","pages":"e1009276"},"PeriodicalIF":0.0,"publicationDate":"2015-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21623996.2015.1009276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34210317","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}

引用次数: 16

Trypanosoma cruzi parasites fight for control of the JAK-STAT pathway by disarming their host. 克氏锥虫通过解除宿主的武装来控制JAK-STAT通路。

JAK-STAT Pub Date : 2015-02-03 eCollection Date: 2014-01-01 DOI: 10.1080/21623996.2015.1012964

Philipp Stahl, Ralph T Schwarz, Françoise Debierre-Grockiego, Thomas Meyer

引用次数: 11

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