Activation of the p42 mitogen-activated protein kinase pathway inhibits Cdc2 activation and entry into M-phase in cycling Xenopus egg extracts
Activation of the p42 mitogen-activated protein kinase pathway inhibits Cdc2 activation and entry into M-phase in cycling Xenopus egg extracts
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DOI：
10.1091/mbc.9.2.451
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发表时间：
1998-02-01
影响因子：
3.3
通讯作者：
Shibuya, EK
中科院分区：
文献类型：
--
作者：
Bitangcol, JC;Chau, ASS;Shibuya, EK
我们已经添加了组成型活性MAP激酶/ERK激酶（MEK），促分裂原活化蛋白激酶（MAPK）信号通路的激活剂，在细胞周期的不同时间循环爪蟾卵提取物。如前所述，在进入M期期间p42 MAPK活化将细胞周期阻滞在中期。出乎意料的是，p42 MAPK在间期激活抑制进入M期。在这些间期阻滞提取物中，H1激酶活性保持较低，Cdc 2被酪氨酸磷酸化，细胞核继续增大。重组细胞周期蛋白B克服了间期阻滞。在其他实验中，MEK或Mos激活p42 MAPK可抑制cyclin B激活Cdc 2。MEK的特异性抑制剂PD 098059可阻断MEK（QP）和Mos的作用。MOS诱导的P42 MAPK激活不抑制DNA复制。这些结果表明，除了在M期阻滞中p42 MAPK激活的既定作用外，在间期期间p42 MAPK的不适当激活阻止正常进入M期。
We have added constitutively active MAP kinase/ERK kinase (MEK), an activator of the mitogen-activated protein kinase (MAPK) signaling pathway, to cycling Xenopus egg extracts at various times during the cell cycle. p42MAPK activation during entry into M-phase arrested the cell cycle in metaphase, as has been shown previously. Unexpectedly, p42MAPK activation during interphase inhibited entry into M-phase. Ln these interphase-arrested extracts, H1 kinase activity remained low, Cdc2 was tyrosine phosphorylated, and nuclei continued to enlarge. The interphase arrest was overcome by recombinant cyclin B. Ln other experiments, p42MAPK activation by MEK or by Mos inhibited Cdc2 activation by cyclin B. PD098059, a specific inhibitor of MEK, blocked the effects of MEK(QP) and Mos. Mos-induced activation of P42MAPK did not inhibit DNA replication. These results indicate that, in addition to the established role of p42MAPK activation in M-phase arrest, the inappropriate activation of p42MAPK during interphase prevents normal entry into M-phase.