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Differential redox regulation within the PTP superfamily

机译：PTP超家族中的差异氧化还原调节

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The Protein Tyrosine Phosphatase (PTP) family comprises a large and diverse group of enzymes, regulating a range of biological processes through de-phosphorylation of many proteins and lipids. These enzymes share a catalytic mechanism that requires a reduced and reactive cysteine nucleophile, making them potentially sensitive to inactivation and regulation by oxidation. Analysis of ten PTPs identified substantial differences in the sensitivity of these enzymes to oxidation in vitro. More detailed experiments confirmed the following rank order of sensitivity: PTEN and Sac1 > PTPL1/FAP-1 myotubularins. When the apparent sensitivity to oxidation of these PTPs in cells treated with hydrogen peroxide was analysed, this correlated well with the observed sensitivities to oxidation in vitro. These data suggested that different PTPs may fall into at least three different classes with respect to mechanisms of cellular redox regulation. 1. PTEN and Sac1 were readily and reversibly oxidised in vitro and in cells treated with hydrogen peroxide 2. PTPL1 appeared to be resistant to oxidation in cells, correlating with its sensitivity to reduction by glutathione in vitro 3. The myotubularin family of lipid phosphatases was almost completely resistant to oxidation in vitro and in cells. Our results show that sensitivity to reversible oxidation is not a necessary characteristic of the PTPs and imply that such sensitivity has evolved as a regulatory mechanism for some of this large family, but not others. (c) 2007 Elsevier Inc. All rights reserved.
机译：蛋白质酪氨酸磷酸酶（PTP）家族包含大量不同的酶，它们通过许多蛋白质和脂质的去磷酸化作用来调节一系列生物过程。这些酶共有催化机制，需要还原的反应性半胱氨酸亲核试剂，使其对氧化的失活和调节具有潜在的敏感性。对十种PTP的分析确定了这些酶在体外对氧化的敏感性方面的显着差异。更详细的实验证实了以下敏感性排序：PTEN和Sac1> PTPL1 / FAP-1 肌微管蛋白。当分析过氧化氢处理的细胞中这些PTP的表观氧化敏感性时，这与在体外观察到的对氧化的敏感性高度相关。这些数据表明，关于细胞氧化还原调节的机制，不同的PTP可分为至少三个不同的类别。 1. PTEN和Sac1在体外和用过氧化氢处理的细胞中容易被可逆氧化。2. PTPL1对细胞的氧化具有抗性，与其在体外对谷胱甘肽还原的敏感性相关。3.脂蛋白的肌管蛋白家族为在体外和细胞中几乎完全抗氧化。我们的结果表明，对可逆氧化的敏感性不是PTP的必要特征，并且暗示这种敏感性已发展成为该大家族中某些家族而非其他家族的调节机制。 （c）2007 Elsevier Inc.保留所有权利。

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