Myristoylated alanine rich C kinase substrate/Activated Cdc42-associated kinase 1 regulates cortactin to promote neutrophil elastase-induced mucin secretion in airway epithelial cells
crossref(2022)
摘要
Abstract Purpose Mucus secretion is excessively increased in airway epithelial cells in pathological states. This process is related to the cytoskeleton and the increase in exocytosis sites, but the movement of secreted molecules and how secretion increases remain unclear. In this study, we examined the potential role of myristoylated alanine rich C kinase substrate (MARCKS) and the cortical actin-binding protein cortactin in airway mucin secretion. Also we investigated the effect of activated Cdc42-associated kinase 1 (ACK1) in this process. Methods Human airway epithelial cells were treated with neutrophil elastase (NE) after treatment with siRNA to specifically knock down MARCKS, ACK1 and cortactin expression. The expression and localization of cortactin and MARCKS were observed by western blotting and immunofluorescence, and the phosphorylated forms of MARCKS, cortactin and ACK1 were detected. The interaction of cortactin and ACK1 was analyzed by coimmunoprecipitation. MUC5AC protein expression was measured by ELISAs. Results Phosphorylated cortactin was highly expressed, mainly at the cell membrane, after NE stimulation, and phosphorylated MARCKS was mainly expressed in the cytoplasm. Coimmunoprecipitation revealed that ACK1 and cortactin interacted with each other. Knockdown of MARCKS suppressed phosphorylation of cortactin, while cortactin siRNA had no significant effect on MARCKS activation. Knockdown of MARCKS, cortactin and ACK1 by siRNA attenuated the phosphorylation of cortactin and reduced MUC5AC secretion. Conclusion These results suggest that both cortactin and MARCKS are involved in MUC5AC secretion by increasing F-actin polymerization and translocation and that MARCKs and ACK1 play an important role in the activation of cortactin.
更多查看译文
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要