Desmosome remodeling is crucial for epidermal regeneration, differentiation and wound healing. It is mediated by adapting the composition and by posttranslational modifications of constituent proteins. We have previously demonstrated that plakophilin 1 (PKP1) mediates strong adhesion in suprabasal keratinocytes which is negatively regulated by insulin-like growth factor-1 (IGF1) signaling. The importance of PKP3 for epidermal adhesion is incompletely understood. Here, we identify a major role of epidermal growth factor (EGF) but not IGF1 signaling in PKP3 recruitment to the plasma membrane to facilitate desmosome assembly. We find that ribosomal S6 kinase (RSK) associates with and phosphorylates PKP3 which promotes PKP3 association with desmosomes downstream of the EGF-receptor. Knockdown of RSKs as well as mutation of a RSK phosphorylation site in PKP3 interfered with desmosome formation, maturation and adhesion. Our findings implicate a coordinate action of distinct growth factors in the control of adhesive properties of desmosomes through modulation of PKPs in a context-dependent manner.

中文翻译：

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核糖体 S6 激酶对 Plakophilin 3 进行磷酸化，支持桥粒组装。

桥粒重塑对于表皮再生、分化和伤口愈合至关重要。它是通过调整组成和组成蛋白的翻译后修饰来介导的。我们之前已经证明，plakophilin 1 (PKP1) 介导基底上角质形成细胞中的强粘附，而这种粘附受到胰岛素样生长因子 1 (IGF1) 信号传导的负调节。PKP3 对于表皮粘附的重要性尚不完全清楚。在这里，我们确定了表皮生长因子 (EGF) 而不是 IGF1 信号在 PKP3 募集到质膜以促进桥粒组装中的主要作用。我们发现核糖体 S6 激酶 (RSK) 与 PKP3 结合并磷酸化 PKP3，从而促进 PKP3 与 EGF 受体下游桥粒的结合。RSK 的敲低以及 PKP3 中 RSK 磷酸化位点的突变会干扰桥粒的形成、成熟和粘附。我们的研究结果表明，不同的生长因子通过以上下文相关的方式调节 PKP 来控制桥粒的粘附特性。