The nucleus, a site for signal termination by sequestration and inactivation of p42/p44 MAP kinases.
The nucleus, a site for signal termination by sequestration and inactivation of p42/p44 MAP kinases.
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发表时间：
2001-10
影响因子：
4
通讯作者：
Véronique Volmat;Montserrat Camps;Steve Arkinstall;Jacques Pouysségur;P. Lenormand
中科院分区：
文献类型：
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作者：
Véronique Volmat;Montserrat Camps;Steve Arkinstall;Jacques Pouysségur;P. Lenormand
我们先前报道，核转位是p42/p44 MAPKs(ERKs)丝裂原信号转导所必需的。在这里，我们显示，在长期刺激期间，p42/p44 MAPK在细胞核内积聚时变得不活跃。这种失活是通过磷酸特异性免疫染色和核p42/p44 MAPKs底物HIF-1α的去磷酸化来监测的。负责p42/p44MAPKs核失活的磷酸酶是新合成的，具有酪氨酸或双特异性，并通过特定的对接位置与p42/p44MAPKs相互作用。可能的候选基因是mkp1/2磷酸酶。此外，在静止期和血清刺激的细胞中，p42/p44MAPK在胞浆和胞核之间永久穿梭。因此，细胞核是有丝分裂信号终止的关键部位：(1)p42/p44MAPK的核隔离，远离它们的细胞质激活剂MEK；(2)特定的核磷酸酶去磷酸化。
We previously reported that nuclear translocation is essential for p42/p44 MAPKs (ERKs) mitogenic signaling. Here we show that, during long-term stimulation, p42/p44 MAPKs become inactive while they accumulate in the nucleus. This inactivation was monitored by phospho-specific immunostaining and dephosphorylation of a nuclear p42/p44 MAPKs substrate, HIF-1 alpha. The phosphatases responsible for p42/p44 MAPKs nuclear inactivation are neo-synthesized, show tyrosine or dual specificity, and interact with p42/p44 MAPKs via a specific docking site. Likely candidates are MKP1/2 phosphatases. In addition, p42/p44 MAPKs permanently shuttle between the cytoplasm and the nucleus in quiescent as well as in serum stimulated cells. Hence, the nucleus is a critical site for mitogenic signal termination by: (1) nuclear sequestration of p42/p44 MAPKs away from MEK, their cytoplasmic activator; and (2) dephosphorylation by specific nuclear phosphatases.