Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b
Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b
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DOI：
10.1016/s1074-7613(00)80449-5
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发表时间：
1997-06-01
期刊：
影响因子：
32.4
通讯作者：
Han, JH
中科院分区：
文献类型：
--
作者：
Huang, S;Jiang, Y;Han, JH
Fas/APO-1（CD95）连接激活程序性细胞死亡，这是一个在宿主免疫反应成熟中起重要作用的细胞过程。我们发现，特定MAP激酶激酶（MKK） MKK6b的激活对于fas诱导的Jurkat T细胞凋亡是必要和充分的。MKK6b激活发生在白细胞介素-1转换酶样（ICE-like）蛋白酶的下游，而MKK6b执行凋亡途径需要ICE-和cpp32样蛋白酶。令人惊讶的是，已知的MKK6b底物p38 MAP激酶蛋白不参与Fas/MKK6b介导的细胞凋亡。这些发现表明，MKK6b信号通路存在分化，其中一条激活p38并导致基因表达调控，另一条激活ICE/Ced-3蛋白酶家族并导致细胞死亡。这些研究表明，凋亡途径是由ICE/Ced-3蛋白酶家族和MAP激酶激酶6组成的。
Fas/APO-1(CD95) ligation activates programmed cell death, a cellular process that plays an important role in the maturation of the host immune response. We show that activation of a specific MAP kinase kinase (MKK), MKK6b, is necessary and sufficient for Fas-induced apoptosis of Jurkat T cells. MKK6b activation occurs downstream of an interleukin-1 converting enzyme-like (ICE-like) protease(s), while execution of the apoptotic pathway by MKK6b requires both ICE- and CPP32-like proteases. Surprisingly, the p38 MAP kinase protein, a known substrate of MKK6b, does not participate in Fas/MKK6b-mediated apoptosis. These findings indicate a divergence of the MKK6b signaling pathways, one of which activates p38 and leads to regulation of gene expression, and one of which activates the ICE/Ced-3 family of proteases and leads to cell death. These studies represent a demonstration of an apoptotic pathway that is comprised of both the ICE/Ced-3 family of proteases and MAP kinase kinase 6.