ERK-MAPK drives lamellipodia protrusion by activating the WAVE2 regulatory complex.
ERK-MAPK drives lamellipodia protrusion by activating the WAVE2 regulatory complex.
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ERK-MAPK通过激活Wave2调节复合物来驱动层状脂蛋白突出。
DOI：
10.1016/j.molcel.2011.02.031
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发表时间：
2011-03-18
期刊：
影响因子：
16
通讯作者：
Blenis J
中科院分区：
文献类型：
--
作者：
Mendoza MC;Er EE;Zhang W;Ballif BA;Elliott HL;Danuser G;Blenis J
细胞运动开始于前缘突起，其由新生粘连稳定并由成熟粘连缩回。ERK-MAPK（细胞外信号调节激酶原活化蛋白激酶）定位于突起和粘连，但它如何调节运动性尚不清楚。我们证明ERK控制突起的启动和突起的速度。片状伪足突起通过WRC（WAVE 2调节复合物）产生，其激活Arp 2/3肌动蛋白成核剂用于肌动蛋白组装。WRC必须被磷酸化才能被激活，但调节其分子间变化和膜募集的位点和激酶尚不清楚。我们发现ERK与WRC共同定位在片状脂质体的前缘，并直接磷酸化两个WRC组件：WAVE 2和Abi 1。磷酸化是细胞突起过程中WRC与Arp 2/3和肌动蛋白相互作用所必需的。因此，ERK与WRC活化和肌动蛋白聚合协调粘附拆卸，以促进细胞迁移过程中的生产性前沿进展。
Cell movement begins with a leading edge protrusion, which is stabilized by nascent adhesions and retracted by mature adhesions. The ERK-MAPK (extracellular signal regulated kinasemitogen-activated protein kinase) localizes to protrusions and adhesions, but how it regulates motility is not understood. We demonstrate ERK controls protrusion initiation and protrusion speed. Lamellipodial protrusions are generated via the WRC (WAVE2 Regulatory Complex), which activates the Arp2/3 actin nucleator for actin assembly. The WRC must be phosphorylated to be activated, but the sites and kinases that regulate its intermolecular changes and membrane recruitment are unknown. We show ERK co-localizes with the WRC at lamellipodial leading edges and directly phosphorylates two WRC components: WAVE2 and Abi1. The phosphorylations are required for functional WRC interaction with Arp2/3 and actin during cell protrusion. Thus, ERK coordinates adhesion disassembly with WRC activation and actin polymerization to promote productive leading edge advancement during cell migration.
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影响因子：
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