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 Ser⁷⁸ and Ser⁸² 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-α 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.

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。在通过p38 MAPK激活MK2之后，HSP27被MK2磷酸化和解聚，从而增加了细胞迁移并直接干扰凋亡信号级联反应。Sec6是囊外复合物的组成部分之一，它是一种进化上保守的8蛋白复合物。尽管多项研究表明Sec6参与了多种细胞生理功能，但在细胞迁移和凋亡过程中Sec6与HSP27或p38 MAPK之间的关系仍然不清楚。在本研究中，我们观察到Sec6通过激活MAPK激酶3/6（MKK3 / 6）增强p38 MAPK的磷酸化。而且，⁷⁸和Ser ⁸²位点通过抑制激活的MK2。此外，通过Sec6敲低的磷酸化HSP27或p38 MAPK的减少抑制了细胞迁移并促进了肿瘤坏死因子-α和环己酰亚胺治疗后的细胞凋亡。本研究表明，Sec6通过激活HSP27或p38 MAPK磷酸化参与细胞迁移的增强和细胞凋亡的抑制。