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白细胞介素-6信号转导分子gp130的框间1/2区域中的单个氨基酸取代(色氨酸(666)→丙氨酸)消除了JAK1的结合,并显著损害信号转导。

A single amino acid substitution (Trp(666)-->Ala) in the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction.

作者信息

Haan C, Hermanns H M, Heinrich P C, Behrmann I

机构信息

Department of Biochemistry, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.

出版信息

Biochem J. 2000 Jul 1;349(Pt 1):261-6. doi: 10.1042/0264-6021:3490261.

DOI:10.1042/0264-6021:3490261
PMID:10861237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1221146/
Abstract

gp130 is the common signal-transducing receptor chain of interleukin (IL)-6-type cytokines. Here we describe, for the first time, a single amino acid substitution (Trp(666)-->Ala) in the membrane-proximal interbox1/2 region that abrogates activation of STAT (signal transducer and activator of transcription) transcription factors and the proliferative response of pro-B-cell transfectants. Moreover, association of the Janus kinase JAK1 is prevented. No signalling of heterodimeric IL-5 receptor (IL-5R)/gp130 chimaeras occurs in COS-7 cells, even when only a single cytoplasmic chain of a gp130 dimer contains the Trp(666)Ala mutation, indicating that it acts dominantly.

摘要

gp130是白细胞介素(IL)-6型细胞因子的共同信号转导受体链。在此我们首次描述了膜近端框间1/2区域的一个单氨基酸取代(色氨酸(Trp)(666)→丙氨酸(Ala)),该取代消除了信号转导子和转录激活子(STAT)转录因子的激活以及前B细胞转染子的增殖反应。此外,Janus激酶JAK1的结合也被阻止。即使gp130二聚体中只有一条胞质链含有Trp(666)Ala突变,异源二聚体白细胞介素-5受体(IL-5R)/gp130嵌合体在COS-7细胞中也不会发生信号传导,这表明该突变起主导作用。

相似文献

1
A single amino acid substitution (Trp(666)-->Ala) in the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction.白细胞介素-6信号转导分子gp130的框间1/2区域中的单个氨基酸取代(色氨酸(666)→丙氨酸)消除了JAK1的结合,并显著损害信号转导。
Biochem J. 2000 Jul 1;349(Pt 1):261-6. doi: 10.1042/0264-6021:3490261.
2
Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation.白细胞介素-6信号转导子gp130与Janus激酶1相互作用的结构要求:该受体对激酶激活至关重要。
Biochem J. 2002 Jan 1;361(Pt 1):105-11. doi: 10.1042/0264-6021:3610105.
3
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本文引用的文献

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The cytoplasmic tyrosine motifs in full-length glycoprotein 130 have different roles in IL-6 signal transduction.全长糖蛋白130中的细胞质酪氨酸基序在白细胞介素-6信号转导中具有不同作用。
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Contributions of leukemia inhibitory factor receptor and oncostatin M receptor to signal transduction in heterodimeric complexes with glycoprotein 130.白血病抑制因子受体和制瘤素M受体在与糖蛋白130形成的异二聚体复合物中对信号转导的作用。
J Immunol. 1999 Dec 15;163(12):6651-8.
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Activation of STAT5 by IL-4 relies on Janus kinase function but not on receptor tyrosine phosphorylation, and can contribute to both cell proliferation and gene regulation.白细胞介素-4对信号转导及转录激活因子5(STAT5)的激活依赖于Janus激酶的功能,而非受体酪氨酸磷酸化,并且它既能促进细胞增殖,也能参与基因调控。
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Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression.通过白细胞介素-6信号转导受体蛋白gp130激活蛋白酪氨酸磷酸酶SHP2需要酪氨酸激酶Jak1,并限制急性期蛋白的表达。
Biochem J. 1998 Nov 1;335 ( Pt 3)(Pt 3):557-65. doi: 10.1042/bj3350557.
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Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway.通过gp130/Jak/STAT途径的白细胞介素-6型细胞因子信号传导。
Biochem J. 1998 Sep 1;334 ( Pt 2)(Pt 2):297-314. doi: 10.1042/bj3340297.
9
Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses.Jak1基因的破坏证明了Jaks在细胞因子诱导的生物学反应中具有必需且不可替代的作用。
Cell. 1998 May 1;93(3):373-83. doi: 10.1016/s0092-8674(00)81166-6.
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Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta.确定白细胞介素-2(IL-2)受体β链中对Jak1和Jak3结合重要的区域。Jak3不依赖Jak1向IL-2Rβ的功能性募集。
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