Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases.
Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases.
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DOI：
10.3390/molecules23020395
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发表时间：
2018-02-12
期刊：
影响因子：
--
通讯作者：
Pulido R
中科院分区：
文献类型：
--
作者：
Hendriks W;Bourgonje A;Leenders W;Pulido R
信号转导蛋白中磷酸酪氨酸含量的适当控制对于正常细胞行为是必不可少的，并且在许多病理中丢失。目前，使疾病状态中异常酪氨酸磷酸化水平正常化的尝试涉及应用抑制酪氨酸激酶（TK）的小化合物或添加生长因子或其模拟物以增强受体型TK活性。靶向TK酶对应物（蛋白酪氨酸磷酸酶（PTP）的多酶家族）的治疗仍然缺乏，尽管它们无可争议地参与人类疾病。PTP催化核心的保守结构使直接调节PTP活性的努力受挫，这就提供了关于靶特异性的令人生畏的问题。然而，多年来，许多不同的蛋白质相互作用为基础的调控机制，控制PTP活动已被发现，提供替代的可能性，以控制PTP个别。在这里，我们回顾这些监管原则，讨论现有的生物制剂和蛋白质类化合物，影响PTP活性，并提到未来的机会，通过这些监管概念药物PTP。
Proper control of the phosphotyrosine content in signal transduction proteins is essential for normal cell behavior and is lost in many pathologies. Attempts to normalize aberrant tyrosine phosphorylation levels in disease states currently involve either the application of small compounds that inhibit tyrosine kinases (TKs) or the addition of growth factors or their mimetics to boost receptor-type TK activity. Therapies that target the TK enzymatic counterparts, the multi-enzyme family of protein tyrosine phosphatases (PTPs), are still lacking despite their undisputed involvement in human diseases. Efforts to pharmacologically modulate PTP activity have been frustrated by the conserved structure of the PTP catalytic core, providing a daunting problem with respect to target specificity. Over the years, however, many different protein interaction-based regulatory mechanisms that control PTP activity have been uncovered, providing alternative possibilities to control PTPs individually. Here, we review these regulatory principles, discuss existing biologics and proteinaceous compounds that affect PTP activity, and mention future opportunities to drug PTPs via these regulatory concepts.
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影响因子：
64.8
作者：
Bilwes, AM;denHertog, J;Noel, JP
通讯作者：
Noel, JP
影响因子：
11
作者：
Buxbaum, J. D.;Georgieva, L.;O'Donovan, M. C.
通讯作者：
O'Donovan, M. C.
影响因子：
4.6
作者：
Bach A;Pedersen SW;Dorr LA;Vallon G;Ripoche I;Ducki S;Lian LY
通讯作者：
Lian LY
DOI：
10.1038/nsb1295-1043
发表时间：
1995-12-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
BARFORD, D;JIA, ZC;TONKS, NK
通讯作者：
TONKS, NK
影响因子：
--
作者：
Arkin MR;Tang Y;Wells JA
通讯作者：
Wells JA