Differential redox regulation within the PTP superfamily
Differential redox regulation within the PTP superfamily
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DOI：
10.1016/j.cellsig.2007.01.026
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发表时间：
2007-07-01
影响因子：
4.8
通讯作者：
Leslie, Nick R.
中科院分区：
文献类型：
--
作者：
Ross, Sarah H.;Lindsay, Yvonne;Leslie, Nick R.
蛋白酪氨酸磷酸酶（PTP）家族包括一个庞大而多样的酶组，通过许多蛋白质和脂质的去磷酸化来调节一系列生物过程。这些酶共有一种催化机制，需要还原和反应性半胱氨酸亲核试剂，使它们对氧化失活和调节潜在敏感。10个PTP的分析确定了这些酶在体外氧化的敏感性的实质性差异。更详细的实验证实了以下敏感性等级顺序：PTEN和Sac 1> PTPL 1/FAP-1 >>肌管蛋白。当分析用过氧化氢处理的细胞中这些PTP对氧化的表观敏感性时，这与观察到的体外氧化敏感性良好相关。这些数据表明，不同的PTP可能属于至少三个不同的类相对于细胞氧化还原调节的机制。1. PTEN和Sac 1在体外和用过氧化氢处理的细胞中容易且可逆地氧化2。PTPL 1似乎对细胞中的氧化具有抗性，这与其在体外对谷胱甘肽还原的敏感性相关3。脂质磷酸酶的肌管蛋白家族在体外和细胞中几乎完全抗氧化。我们的研究结果表明，可逆氧化的敏感性是不是一个必要的特征的PTPs，并意味着这种敏感性已经演变为一个调节机制，这个大家庭的一些，但不是其他人。(c)2007年爱思唯尔公司All rights reserved.
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.