Bruton's tyrosine kinase links the B cell receptor to nuclear factor kappaB activation.
Bruton's tyrosine kinase links the B cell receptor to nuclear factor kappaB activation.
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Bruton的酪氨酸激酶将B细胞受体与核因子Kappab激活联系起来。
DOI：
10.1084/jem.191.10.1735
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发表时间：
2000-05-15
影响因子：
15.3
通讯作者：
Wortis, H H
中科院分区：
文献类型：
--
作者：
Bajpai, U D;Zhang, K;Teutsch, M;Sen, R;Wortis, H H
膜免疫球蛋白M（mIgM）对抗原的识别导致细胞质中一系列复杂的信号传导事件，从而引起基因激活。布鲁顿酪氨酸激酶（BTK）是酪氨酸激酶Tec家族的成员，对于完整传递IgM信号是必不可少的。我们研究了BTK调节转录因子核因子（NF）-κB/Rel家族的能力，因为B细胞对mIgM产生反应需要这些因子的激活。我们发现，在X连锁免疫缺陷（xid）小鼠的B细胞中，IgM介导的但不是CD40介导的NF - κB/Rel核转位和DNA结合显著减少，这些小鼠的btk基因存在R28C突变，该突变产生一种无功能的激酶。这种缺陷部分是由于不能完全降解NF - κB的抑制蛋白IκBα。利用DT40鸡B细胞的BTK缺陷型变体，我们发现野生型或功能获得性突变型BTK的表达，而不是R28C突变型，可以重建NF - κB活性。因此，BTK对于通过B细胞受体激活NF - κB是必不可少的。
The recognition of antigen by membrane immunoglobulin M (mIgM) results in a complex series of signaling events in the cytoplasm leading to gene activation. Bruton's tyrosine kinase (BTK), a member of the Tec family of tyrosine kinases, is essential for the full repertoire of IgM signals to be transduced. We examined the ability of BTK to regulate the nuclear factor (NF)-κB/Rel family of transcription factors, as the activation of these factors is required for a B cell response to mIgM. We found greatly diminished IgM- but not CD40-mediated NF-κB/Rel nuclear translocation and DNA binding in B cells from X-linked immunodeficient (xid) mice that harbor an R28C mutation in btk, a mutation that produces a functionally inactive kinase. The defect was due, in part, to a failure to fully degrade the inhibitory protein of NF-κB, IκBα. Using a BTK-deficient variant of DT40 chicken B cells, we found that expression of wild-type or gain-of-function mutant BTK, but not the R28C mutant, reconstituted NF-κB activity. Thus, BTK is essential for activation of NF-κB via the B cell receptor.