Sec6 enhances cell migration and suppresses apoptosis by elevating the phosphorylation of p38 MAPK, MK2, and HSP27
Sec6 enhances cell migration and suppresses apoptosis by elevating the phosphorylation of p38 MAPK, MK2, and HSP27
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Sec6通过上调p38 MAPK、MK2和HSP27的磷酸化促进细胞迁移和抑制细胞凋亡
DOI：
10.1016/j.cellsig.2018.04.009
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发表时间：
2018-09-01
影响因子：
4.8
通讯作者：
Goto, Kaoru
中科院分区：
文献类型：
--
作者：
Tanaka, Toshiaki;Iino, Mitsuyoshi;Goto, Kaoru
p38丝裂原活化蛋白激酶（p38 MAPK）和MAPK活化蛋白激酶2 （MK2）的信号轴是导致热休克蛋白27 （HSP27）磷酸化的主要途径。p38 MAPK激活MK2后，HSP27被MK2磷酸化解聚，从而增加细胞迁移，直接干扰凋亡信号级联反应。Sec6是胞囊复合体的组成部分之一，是一种进化上保守的8蛋白复合体。尽管多项研究表明Sec6参与多种细胞生理功能，但在细胞迁移和凋亡过程中，Sec6与HSP27或p38 MAPK之间的关系尚不清楚。在本研究中，我们观察到Sec6通过激活MAPK激酶3/6 （MKK3/6）来增加p38 MAPK的磷酸化。此外，通过抑制活化的MK2， Sec6敲低抑制了HSP27在Ser（78）和Ser（82）位点的磷酸化。此外，在肿瘤坏死因子-a和环己亚胺处理后，通过敲低Sec6来减少磷酸化的HSP27或p38 MAPK，抑制细胞迁移并促进细胞凋亡。本研究提示Sec6通过激活HSP27或p38 MAPK磷酸化参与细胞迁移增强和抑制凋亡。
The signaling axis of p38 mitogen-activated protein kinase (p38 MAPK) and MAPK-activated protein kinase 2 (MK2) is the dominant pathway that leads to heat shock protein 27 (HSP27) phosphorylation. After activation of MK2 by p38 MAPK, HSP27 is phosphorylated and depolymerized by MK2, thereby increasing the cell migration and directly interfering with the apoptotic signaling cascades. Sec6 is one of the components of the exocyst complex that is an evolutionarily conserved 8-protein complex. Even though several studies have demonstrated that Sec6 is involved in various cellular physiological functions, the relationship between Sec6 and HSP27 or p38 MAPK during cell migration and apoptosis remains unclear. In the present study, we observed that Sec6 increased the phosphorylation of p38 MAPK through the activation of MAPK kinase 3/6 (MKK3/6). Moreover, Sec6 knockdown suppressed the phosphorylation of HSP27 at Ser(78) and Ser(82) sites via suppression of activated MK2. Furthermore, the reduction of phosphorylated HSP27 or p38 MAPK by Sec6 knockdown suppressed cell migration and promoted apoptosis after treatment with tumor necrosis factor-a and cycloheximide. The present study suggested that Sec6 is involved in the enhancement of cell migration and suppression of apoptosis through the activation of HSP27 or p38 MAPK phosphorylation.