Mechanism of mitosis-specific activation of MEK1

被引:46
作者
Harding, A
Giles, N
Burgess, A
Hancock, JF
Gabrielli, BG
机构
[1] Univ Queensland, Canc Biol Program, Ctr Immunol & Canc Res, Brisbane, Qld 4102, Australia
[2] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4102, Australia
关键词
D O I
10.1074/jbc.M301015200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation of cyclin B-Cdc2 is an absolute requirement for entry into mitosis, but other protein kinase pathways that also have mitotic functions are activated during G(2)/M progression. The MAPK cascade has well established roles in entry and exit from mitosis in Xenopus, but relatively little is known about the regulation and function of this pathway in mammalian mitosis. Here we report a detailed analysis of the activity of all components of the Ras/Raf/MEK/ERK pathway in HeLa cells during normal G(2)/M. The focus of this pathway is the dramatic activation of an endomembrane-associated MEK1 without the corresponding activation of the MEK substrate ERK. This is because of the uncoupling of MEK1 activation from ERK activation. The mechanism of this uncoupling involves the cyclin B-Cdc2-dependent proteolytic cleavage of the N-terminal ERK-binding domain of MEK1 and the phosphorylation of Thr(286). These results demonstrate that cyclin B-Cdc2 activity regulates signaling through the MAPK pathway in mitosis.
引用
收藏
页码:16747 / 16754
页数:8
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