共查询到20条相似文献,搜索用时 15 毫秒
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Zong CS Chan J Levy DE Horvath C Sadowski HB Wang LH 《The Journal of biological chemistry》2000,275(20):15099-15105
Recent evidence indicates that STAT proteins can be activated by a variety of receptor and non-receptor protein-tyrosine kinases. Unlike cytokine-induced activation of STATs, where JAKs are known to play a pivotal role in phosphorylating STATs, the mechanism for receptor protein-tyrosine kinase-mediated activation of STATs remains elusive. In this study, we investigated the activation of STAT proteins by the insulin-like growth factor I receptor (IGF-IR) in vitro and in vivo and assessed the role of JAKs in the process of activation. We found that STAT3, but not STAT5, was activated in response to IGF-I in 293T cells cotransfected with IGF-IR and STAT expression vectors. Moreover, tyrosine phosphorylation of STAT3, JAK1, and JAK2 was increased upon IGF-I stimulation of endogenous IGF-IR in 293T cells transfected with the respective STAT or JAK expression vector. Supporting the observation in 293T cells, endogenous STAT3 was tyrosine-phosphorylated upon IGF-I stimulation in the muscle cell line C2C12 as well as in various embryonic and adult mouse organs during different stages of development. Dominant-negative JAK1 or JAK2 was able to block the IGF-IR-mediated tyrosine phosphorylation of STAT3 in 293T cells. A newly identified family of proteins called SOCS (suppressor of cytokine signaling), including SOCS1, SOCS2, SOCS3 and CIS, was able to inhibit the IGF-I-induced STAT3 activation as well with varying degrees of potency, in which SOCS1 and SOCS3 appeared to have the higher inhibitory ability. Inhibition of STAT3 activation by SOCS could be overcome by overexpression of native JAK1 and JAK2. We conclude that IGF-I/IGF-IR is able to mediate activation of STAT3 in vitro and in vivo and that JAKs are essential for the process of activation. 相似文献
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STAT proteins: from normal control of cellular events to tumorigenesis 总被引:47,自引:0,他引:47
Calò V Migliavacca M Bazan V Macaluso M Buscemi M Gebbia N Russo A 《Journal of cellular physiology》2003,197(2):157-168
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The STAT family of proteins in cytokine signaling 总被引:7,自引:0,他引:7
Ke Shuai 《Progress in biophysics and molecular biology》1999,71(3-4):405-422
It has now been well established that the STAT family of proteins play important roles in cytokine-mediated specific gene activation. Although significant progress has been made toward the understanding of the structure and function of STATs as well as the regulation of STAT signaling pathways, many important questions remain to be answered. STAT PTPase(s) and STAT serine kinase(s) which play important roles in regulating STAT activity have not been identified. In addition, the molecular mechanisms of the negative regulation of STAT signaling by recently discovered protein inhibitors and the crosstalk between STAT and other signal transduction pathways have not been understood. The JAK/STAT field remains to be challenging and exciting. 相似文献
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Role of the JAK/STAT signal transduction pathway in the regulation of gene expression in CNS 总被引:11,自引:0,他引:11
Dell'Albani P Santangelo R Torrisi L Nicoletti VG Giuffrida Stella AM 《Neurochemical research》2003,28(1):53-64
Over the last 20 years the JAK/STAT signal transduction pathway has been extensively studied. An enormous amount of data on different cell signal transduction pathways is now available. The JAK/STAT signal transduction pathway is one of the intracellular signaling pathways activated by cytokines and growth factors that was first studied in the hematopoietic system, but recent data demonstrate that this signal transduction is also greatly utilized by other systems. The JAK/STAT pathway is a signaling cascade that links the activation of specific cell membrane receptors to nuclear gene expression. This review is focused on the role of JAK/STAT signal transduction pathway activation in the central nervous system (CNS). 相似文献
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TANK‐binding kinase 1 and Janus kinase 2 play important roles in the regulation of mitogen‐activated protein kinase phosphatase‐1 expression after toll‐like receptor 4 activation
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Eunji Kim Ju Y. Yoon Jongsung Lee Deok Jeong Jae G. Park Yo H. Hong Ji H. Kim Adithan Aravinthan Jong‐Hoon Kim Jae Y. Cho 《Journal of cellular physiology》2018,233(11):8790-8801
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JAK/STAT信号转导通路的异常激活在多种淋巴瘤的发生发展中发挥重要作用. 该信号通路的抑制剂在淋巴瘤的靶向治疗中具有良好的应用前景.本文对JAK/STAT信号通路与淋巴瘤发生、发展的最新研究进展进行综述,重点介绍该信号通路中各种JAK激酶及STAT分子的异常突变类型,以及它们在各类淋巴瘤形成中的作用、调控机制及其靶向治疗策略,旨在为该信号通路在淋巴瘤发生发展中的影响及作用机制的进一步研究提供借鉴. 相似文献
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Bach EA Ekas LA Ayala-Camargo A Flaherty MS Lee H Perrimon N Baeg GH 《Gene expression patterns : GEP》2007,7(3):323-331
JAK/STAT signaling is essential for a wide range of developmental processes in Drosophila melanogaster. The mechanism by which the JAK/STAT pathway contributes to these processes has been the subject of recent investigation. However, a reporter that reflects activity of the JAK/STAT pathway in all Drosophila tissues has not yet been developed. By placing a fragment of the Stat92E target gene Socs36E, which contains at least two putative Stat92E binding sites, upstream of GFP, we generated three constructs that can be used to monitor JAK/STAT pathway activity in vivo. These constructs differ by the number of Stat92E binding sites and the stability of GFP. The 2XSTAT92E-GFP and 10XSTAT92E-GFP constructs contain 2 and 10 Stat92E binding sites, respectively, driving expression of enhanced GFP, while 10XSTAT92E-DGFP drives expression of destabilized GFP. We show that these reporters are expressed in the embryo in an overlapping pattern with Stat92E protein and in tissues where JAK/STAT signaling is required. In addition, these reporters accurately reflect JAK/STAT pathway activity at larval stages, as their expression pattern overlaps that of the activating ligand unpaired in imaginal discs. Moreover, the STAT92E-GFP reporters are activated by ectopic JAK/STAT signaling. STAT92E-GFP fluorescence is increased in response to ectopic upd in the larval eye disc and mis-expression of the JAK kinase hopscotch in the adult fat body. Lastly, these reporters are specifically activated by Stat92E, as STAT92E-GFP reporter expression is lost cell-autonomously in stat92E homozygous mutant tissue. In sum, we have generated in vivo GFP reporters that accurately reflect JAK/STAT pathway activation in a variety of tissues. These reporters are valuable tools to further investigate and understand the role of JAK/STAT signaling in Drosophila. 相似文献
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Regulation of cytokine signaling pathways by PIAS proteins 总被引:3,自引:0,他引:3
Shuai K 《Cell research》2006,16(2):196-202