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首页> 外文期刊>Cellular Signalling >PKC delta stimulates macropinocytosis via activation of SSH1-cofilin pathway
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PKC delta stimulates macropinocytosis via activation of SSH1-cofilin pathway

机译：PKC Delta通过SSH1-Cofilin途径的激活刺激大毒细胞增生症

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Macropinocytosis is an actin-dependent endocytic mechanism mediating internalization of extracellular fluid and associated solutes into cells. The present study was designed to identify the specific protein kinase C (PKC) isoform(s) and down-stream effectors regulating actin dynamics during macropinocytosis. We utilized various cellular and molecular biology techniques, pharmacological inhibitors and genetically modified mice to study the signaling mechanisms mediating macropinocytosis in macrophages. The qRT-PCR experiments identified PKC delta as the predominant PKC isoform in macrophages. Scanning electron microscopy and flow cytometry analysis of FITC-dextran internalization demonstrated the functional role of PKC delta in phorbol ester- and hepatocyte growth factor (HGF)-induced macropinocytosis. Western blot analysis demonstrated that phorbol ester and HGF stimulate activation of slingshot phosphatase homolog 1 (SSH1) and induce cofilin Ser-3 dephosphorylation via PKC delta in macrophages. Silencing of SSH1 inhibited cofilin dephosphorylation and macropinocytosis stimulation. Interestingly, we also found that incubation of macrophages with BMS-5, a potent inhibitor of LIM kinase, does not stimulate macropinocytosis. In conclusion, the findings of the present study demonstrate a previously unidentified mechanism by which PKC delta via activation of SSH1 and cofilin dephosphorylation stimulates membrane ruffle formation and macropinocytosis. The results of the present study may contribute to a better understanding of the regulatory mechanisms during macrophage macropinocytosis.
机译：大型细胞增生是一种诱导型内吞作用机制，所述细胞外液体的内化和相关溶质介导细胞。本研究旨在鉴定在癌细胞增生症期间调节肌动蛋白动态的特定蛋白激酶C（PKC）同种型和下游效应。我们利用各种细胞和分子生物学技术，药理学抑制剂和遗传修饰的小鼠来研究介导巨噬细胞癌细胞增生的信号传导机制。 QRT-PCR实验将PKC Delta鉴定为巨噬细胞中的主要PKC同种型。扫描电子显微镜和流式细胞术分析FitC-葡聚糖内化展示了PKC Delta在Phorbol酯和肝细胞生长因子（HGF）诱导的大磷梗死中的功能作用。 Western印迹分析证明，菲尔伯酯和HGF刺激弹性磷酸酶同源物1（SSH1）的活化，并通过PKC Delta在巨噬细胞中诱导Cocilin Ser-3去磷酸化。 SSH1的沉默抑制了Cofilin去磷酸化和大毒细胞增生刺激。有趣的是，我们还发现，用BMS-5孵育巨噬细胞，Lim激酶的有效抑制剂，不刺激大毒素细胞症。总之，本研究的发现证明了一种先前未识别的机制，通过激活SSH1和辛苷去磷酸化刺激膜缠绕形成和大毒细胞增生症。本研究的结果可能有助于更好地理解巨噬细胞癌细胞病过程中的调节机制。

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