Tribbles 2 (Trib2) is a novel regulator of toll-like receptor 5 signaling.
Tribbles 2 (Trib2) is a novel regulator of toll-like receptor 5 signaling.
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DOI：
10.1002/ibd.22883
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发表时间：
2012-05
影响因子：
4.9
通讯作者：
Podolsky, Daniel K.
中科院分区：
文献类型：
--
作者：
Wei, Shu-Chen;Rosenberg, Ian M.;Cao, Zhifang;Huett, Alan S.;Xavier, Ramnik J.;Podolsky, Daniel K.
Toll样受体（TLR）由多种细胞表达，包括肠上皮细胞。然而，通过TLR调节先天反应的调节剂的全谱尚未被描绘。Tribbles（Trib）是一类高度保守的激酶样蛋白家族。我们试图阐明Trib 2在TLR信号通路中的作用。Trib 2 mRNA和蛋白水平分别通过定量PCR和Western blot分析。免疫组化染色检测Trib 2在人组织中的表达。通过NF-κB报告基因分析在上皮细胞中评估Trib 2在NF-κB途径中的参与。通过质谱法鉴定与Trib 2相互作用的蛋白质，并通过免疫沉淀法确认。使用截短的构建体映射Trib 2功能所必需的结构域。Trib 2表达在炎症性肠病患者的活动性炎症组织中降低。Trib 2在人和小鼠结肠上皮以及免疫细胞中表达，并且其在上皮中的表达可通过TLR 5配体刺激以配体依赖性方式诱导。Trib 2抑制TLR 5介导的TRAF 6下游NF-κB的活化。Trib 2选择性调节MAPK通路p38和JNK，但不调节p44/p42（ERK 1/2）。NF-κB2（p100）被鉴定为调节TLR 5信号通路的Trib 2结合伴侣，导致NF-κB活性抑制。Trib 2激酶样结构域中的残基158-177是Trib 2功能所需的。这些观察结果表明，Trib 2是TLR 5信号通路中的一种新型调节剂，Trib 2的表达改变可能在IBD中起作用。
Toll-like receptors (TLRs) are expressed by a variety of cells, including intestinal epithelia. However, the full spectrum of regulators modulating innate responses via TLRs has not been delineated. Tribbles (Trib) have been identified as a highly conserved family of kinase-like proteins. We sought to clarify the role of Trib2 in the TLR signaling pathway. Trib2 mRNA and protein levels were analyzed by quantitative PCR and Western blot, respectively. Immunohistochemical staining was used to determine the expression of Trib2 in human tissue. Involvement of Trib2 in NF-κB pathways was assessed in epithelial cells by NF-κB reporter assay. Proteins that interacted with Trib2 were identified by mass spectrometry and confirmed by immunoprecipitation. The domain essential for Trib2 function was mapped using truncated constructs. Trib2 expression is decreased in active inflamed tissue from patients with inflammatory bowel disease. Trib2 is expressed in human and mouse colonic epithelium as well as immune cells, and its expression in epithelium is inducible in a ligand-dependent manner by TLR5 ligand stimulation. Trib2 inhibits TLR5-mediated activation of NF-κB downstream of TRAF6. Trib2 selectively modulates MAPK pathways p38 and JNK but not p44/p42 (ERK1/2). NF-κB2 (p100) was identified as a Trib2 binding partner in regulating the TLR5 signaling pathway that leads to inhibition of NF-κB activity. Residues 158–177 in the Trib 2 kinase-like domain are required for Trib2 function. These observations indicate that Trib2 is a novel regulator in the TLR5 signaling pathway and altered expression of Trib2 may play a role in IBD.
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影响因子：
9.9
作者：
Oda, Kanae;Kitano, Hiroaki
通讯作者：
Kitano, Hiroaki
DOI：
10.1111/j.1432-1033.1997.t01-1-00660.x
发表时间：
1997-09-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Wilkin, F;SuarezHuerta, N;Maenhaut, C
通讯作者：
Maenhaut, C
DOI：
10.1196/annals.1326.009
发表时间：
2006-01-01
期刊：
INFLAMMATORY BOWEL DISEASE: GENETICS, BARRIER FUNCTION, IMMUNOLOGIC MECHANISMS, AND MICROBIAL PATHWAYS
影响因子：
--
作者：
Egan, Laurence J.;Toruner, Murat
通讯作者：
Toruner, Murat
影响因子：
11.4
作者：
Cheung, PCF;Campbell, DG;Cohen, P
通讯作者：
Cohen, P
影响因子：
30.5
作者：
Ishimaru, Naozumi;Kishimoto, Hidehiro;Sprent, Jonathan
通讯作者：
Sprent, Jonathan