Bcl10 is a positive regulator of antigen receptor-induced activation of NF-κB and neural tube closure
Bcl10 is a positive regulator of antigen receptor-induced activation of NF-κB and neural tube closure
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DOI：
10.1016/s0092-8674(01)00189-1
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发表时间：
2001-01-12
期刊：
影响因子：
64.5
通讯作者：
Mak, TW
中科院分区：
文献类型：
--
作者：
Ruland, J;Duncan, GS;Mak, TW
Bcl 10是一种在MALT淋巴瘤中从t（1; 14）（p22; q32）断点鉴定的含CARD的蛋白，已显示在体外诱导细胞凋亡并激活NF-κ B。我们发现三分之一的bcl10（-/-）胚胎发育为露脑畸形，导致胚胎死亡。令人惊讶的是，bcl10（-/-）细胞在体内和体外对各种凋亡刺激保持敏感性。然而，存活的bcl10（-/-）小鼠严重免疫缺陷，bcl10（-/-）淋巴细胞在抗原受体或PMA/lonomycin诱导的活化中有缺陷。早期酪氨酸磷酸化，MAPK和AP-1激活，和Ca2+信号在突变淋巴细胞中是正常的，但抗原受体诱导的NF-κ B激活是不存在的。因此，Bcl 10作为淋巴细胞增殖的正调节剂发挥作用，其特异性地将B和T细胞中的抗原受体信号传导与NF-κ B活化连接。
Bcl10, a CARD-containing protein identified from the t(1;14)(p22;q32) breakpoint in MALT lymphomas, has been shown to induce apoptosis and activate NF-kappaB in vitro. We show that one-third of bcl10(-/-) embryos developed exencephaly, leading to embryonic lethality. Surprisingly, bcl10(-/-) cells retained susceptibility to various apoptotic stimuli in vivo and in vitro. However, surviving bcl10(-/-) mice were severely immunodeficient and bcl10(-/-) lymphocytes are defective in antigen receptor or PMA/lonomycin-induced activation. Early tyrosine phosphorylation, MAPK and AP-1 activation, and Ca2+ signaling were normal in mutant lymphocytes, but antigen receptor-induced NF-kappaB activation was absent. Thus, Bcl10 functions as a positive regulator of lymphocyte proliferation that specifically connects antigen receptor signaling in B and T cells to NF-kappaB activation.