Protein tyrosine phosphatases (PTPs) can be regulated by several redox-dependent mechanisms and control growth factor-activated receptor tyrosine kinase phosphorylation cascades. Reversible oxidation of PTPs is counteracted by reductive enzymes, including thioredoxin (Trx) and Trx-related protein of 14 kDa (TRP14), keeping PTPs in their reduced active states. Different modes of oxidative inactivation of PTPs concomitant with assessment of activating reduction have been little studied in direct comparative analyses. Determining PTP1B activities, we here compared the potency of inactivation by bicarbonate-assisted oxidation using H₂O₂ with that of polysulfide-mediated inactivation. Inactivation of pure PTP1B was about three times more efficient with polysulfides as compared to the combination of bicarbonate and H₂O₂. Bicarbonate alone had no effect on PTP1B, neither with nor without a combination with polysulfides, thus strengthening the notion that bicarbonate-assisted H₂O₂-mediated inactivation of PTP1B involves formation of peroxymonocarbonate. Furthermore, PTP1B was potently protected from polysulfide-mediated inactivation by either TRP14 or Trx1, in contrast to the inactivation by bicarbonate and H₂O₂. Comparing reductive activation of polysulfide-inactivated PTP1B with that of bicarbonate- and H₂O₂-treated enzyme, we found Trx1 to be more potent in reactivation than TRP14. Altogether we conclude that inactivation of PTP1B by polysulfides displays striking qualitative differences compared to that by H₂O₂ together with bicarbonate, also with regard to maintenance of PTP1B activity by either Trx1 or TRP14.

中文翻译：

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还原性Trx1或TRP14酶系统在多硫化物或H2O2和碳酸氢盐的氧化挑战下对PTP1B活性的保护的质性差异

蛋白质酪氨酸磷酸酶（PTP）可以通过几种氧化还原依赖性机制来调节，并控制生长因子激活的受体酪氨酸激酶磷酸化级联反应。PTP的可逆氧化被还原酶（包括硫氧还蛋白（Trx）和14 kDa的Trx相关蛋白（TRP14）抵消，使PTP保持其还原态。在直接比较分析中，对PTP氧化失活的不同模式以及活化还原的评估很少进行研究。为了确定PTP1B的活性，我们在这里比较了使用H ₂ O _2的碳酸氢盐辅助氧化灭活的能力。与多硫化物介导的失活有关。与碳酸氢盐和H ₂ O ₂的组合相比，多硫化物对纯PTP1B的灭活效率大约高三倍。单独使用碳酸氢盐对PTP1B均无影响，无论是否与多硫化物结合均不起作用，因此加强了以下观念：碳酸氢盐辅助H ₂ O ₂介导的PTP1B失活涉及过氧一碳酸氢盐的形成。此外，与被碳酸氢盐和H ₂ O ₂灭活相反，PTP1B被TRP14或Trx1有效地保护免受多硫化物介导的灭活作用。比较多硫化物灭活的PTP1B与碳酸氢盐和H的还原活化_在2 O ₂处理的酶中，我们发现Trx1在重新激活方面比TRP14更有效。总而言之，我们得出结论，与H ₂ O ₂和碳酸氢盐一起，多硫化物对PTP1B的灭活表现出惊人的质量差异，在Trx1或TRP14维持PTP1B活性方面也是如此。