The extra-cellular signal regulated kinases ERK1 and ERK2 segregate displaying distinct spatiotemporal characteristics in activated mast cells
The extra-cellular signal regulated kinases ERK1 and ERK2 segregate displaying distinct spatiotemporal characteristics in activated mast cells
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DOI：
10.1016/j.bbamcr.2013.04.016
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发表时间：
2013-09-01
影响因子：
5.1
通讯作者：
Sagi-Eisenberg, Ronit
中科院分区：
文献类型：
--
作者：
Bar-Gill, Anat Benado;Efergan, Adi;Sagi-Eisenberg, Ronit
ERK1和ERK2是高度同源的亚型，经常在调节细胞功能中发挥冗余作用。我们分析了静止和激活肥大细胞中ERK1和ERK2的时空模式。引人注目的是，我们发现了这些激酶的不同途径。ERK1定位于细胞质并在细胞活化和激酶磷酸化后转移到细胞核。相反，在静息细胞中，ERK2分布在细胞质之间和微管组织中心（MTOC）附近，并在细胞触发后进一步积聚在核内体周围区域。ERK2的核周围累积与磷酸化无关，需要一个完整的微管网络，并通过神经元钙传感器-1 （NCS-1）的过表达显著增强。我们还发现-微管蛋白和磷脂酰肌醇4激酶β (PI4K β)， NCS-1的下游效应，作为ERK2的新伙伴蛋白。综上所述，我们的研究结果表明ERK1和ERK2在肥大细胞中具有非冗余功能，并暗示NCS-1和PI4K β是ERK2运输的调节因子。(C) 2013 Elsevier B.V.版权所有
ERK1 and ERK2 are highly homologous isoforms that often play redundant roles in regulating cellular functions. We analyzed the spatiotemporal patterns of ERK1 and ERK2 in resting and activated mast cells. Strikingly, we identified distinct pathways for these kinases. ERK1 localized to the cytosol and translocated to the nucleus upon cell activation and kinase phosphorylation. In contrast, ERK2 distributed between the cytosol and near the microtubule organizing center (MTOC) in resting cells and accumulated further at a pericentrosomal region upon cell trigger. Pericentrosomal accumulation of ERK2 was phosphorylation independent, required an intact microtubule network and was significantly enhanced by the overexpression of Neuronal Calcium Sensor-1 (NCS-1). We also identified gamma-tubulin and phosphatidylinositol 4 kinase beta (PI4K beta), a downstream effector of NCS-1, as novel partner proteins of ERK2. Taken together, our results imply non-redundant functions of ERK1 and ERK2 in mast cells and implicate NCS-1 and PI4K beta as regulators of ERK2 trafficking. (C) 2013 Elsevier B.V. All rights reserved.