Redox-mediated signal transduction depends on the enzymatic production of second messengers such as hydrogen peroxide, nitric oxide and hydrogen sulfite, as well as specific, reversible redox modifications of cysteine-residues in proteins. So-called thiol switches induce for instance conformational changes in specific proteins that regulate cellular pathways e.g., cell metabolism, proliferation, migration, gene expression and inflammation. Reduction, oxidation and disulfide isomerization are controlled by oxidoreductases of the thioredoxin family, including thioredoxins, glutaredoxins, peroxiredoxins and protein dsisulfide isomerases. These proteins are located in different cellular compartments, interact with substrates and catalyze specific reactions. Interestingly, some of these proteins are released by cells. Their extracellular functions and generally extracellular redox control have been widely underestimated. Here, we give an insight into extracellular redox signaling, extracellular thiol switches and their regulation by secreted oxidoreductases and thiol-isomerases, a topic whose importance has been scarcely studied so far, likely due to methodological limitations. We focus on the secreted redox proteins and characterized thiol switches in the ectodomains of membrane proteins, such as integrins and the metalloprotease ADAM17, which are among the best-characterized proteins and discuss their underlying mechanisms and biological implications.

中文翻译：

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膜蛋白中的硫醇开关 - 细胞生物学中的细胞外氧化还原调节

氧化还原介导的信号转导取决于第二信使的酶促产生，例如过氧化氢、一氧化氮和亚硫酸氢盐，以及蛋白质中半胱氨酸残基的特异性、可逆氧化还原修饰。所谓的硫醇开关诱导例如调节细胞途径的特定蛋白质的构象变化，例如细胞代谢、增殖、迁移、基因表达和炎症。还原、氧化和二硫化物异构化由硫氧还蛋白家族的氧化还原酶控制，包括硫氧还蛋白、谷氧还蛋白、过氧还蛋白和蛋白质双硫键异构酶。这些蛋白质位于不同的细胞区室中，与底物相互作用并催化特定反应。有趣的是，其中一些蛋白质是由细胞释放的。它们的细胞外功能和通常的细胞外氧化还原控制被广泛低估。在这里，我们深入了解细胞外氧化还原信号、细胞外硫醇开关及其通过分泌的氧化还原酶和硫醇异构酶的调节，该主题的重要性迄今为止很少被研究，可能是由于方法学上的限制。我们专注于分泌的氧化还原蛋白和膜蛋白胞外域中的硫醇开关特征，例如整合素和金属蛋白酶 ADAM17，它们是表征最好的蛋白质之一，并讨论了它们的潜在机制和生物学意义。细胞外硫醇开关及其通过分泌的氧化还原酶和硫醇异构酶的调节，到目前为止，该主题的重要性几乎没有研究过，可能是由于方法学上的限制。我们专注于分泌的氧化还原蛋白和膜蛋白胞外域中的硫醇开关特征，例如整合素和金属蛋白酶 ADAM17，它们是表征最好的蛋白质之一，并讨论了它们的潜在机制和生物学意义。细胞外硫醇开关及其通过分泌的氧化还原酶和硫醇异构酶的调节，到目前为止，该主题的重要性几乎没有研究过，可能是由于方法学上的限制。我们专注于分泌的氧化还原蛋白和膜蛋白胞外域中的硫醇开关特征，例如整合素和金属蛋白酶 ADAM17，它们是表征最好的蛋白质之一，并讨论了它们的潜在机制和生物学意义。