Role of the amino-terminal domains of MEKKs in the activation of NFκB and MAPK pathways and in the regulation of cell proliferation and apoptosis
Role of the amino-terminal domains of MEKKs in the activation of NFκB and MAPK pathways and in the regulation of cell proliferation and apoptosis
复制标题
DOI：
10.1016/s0898-6568(01)00219-4
复制
发表时间：
2002-02-01
影响因子：
4.8
通讯作者：
Widmann, C
中科院分区：
文献类型：
--
作者：
Bonvin, C;Guillon, A;Widmann, C
丝裂原激活蛋白激酶 (MAPK)/细胞外信号调节激酶 (ERK) 激酶 (MEK) 激酶 (MEKK) 是 MAPK 上游调节剂的丝氨酸/苏氨酸激酶。在这里，MEKK1-4 的氨基末端（N 末端）结构域对不同细胞内信号通路、细胞凋亡的调节的作用。通过比较全长 (FL) MEKK 诱导的反应与仅由激酶结构域诱导的反应来评估细胞增殖。对于每个 MEKK，NFkappaB、ERK MAPK 通路和 c-Jun N 末端激酶 (JNK) MAPK 通路的激活模式在激酶结构域和 FL 形式之间显着不同。同样，细胞增殖和凋亡受到 FL MEKK 和相应激酶结构域的不同调节。我们的数据表明，MEKK 的 N 端结构域决定了各种细胞内信号传导途径和细胞反应的特异性和激活强度。 (C) 2002 Elsevier Science Inc. 保留所有权利。
Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) kinases (MEKKs) are serine/threonine kinases that Eire upstream regulators, of MAPKs. Here, the role of the amino-terminal (N-teminal) domain of MEKK1-4 on the regulation of different intracellular signaling pathways, apoptosis. and cell proliferation has been assessed by comparing the responses induced by the full-length (FL) MEKKs, to those induced by the kinase domains only. For each MEKK, the pattern of activation of NFkappaB, the ERK MAPK pathway, and the c-Jun N-terminal kinase (JNK) MAPK pathway markedly differed between kinase domain and the FL form. Similarly, cell proliferation and apoptosis were differently regulated by the FL MEKK and the corresponding kinase domain. Our data show that the N-terminal domain of the MEKKs determines, the specificity and the strength of activation of various intracellular signaling Pathways and cellular,responses. (C) 2002 Elsevier Science Inc. All rights reserved.