Mitogen-activated protein kinase phosphatase (MKP)-1 in immunology, physiology, and disease.
Mitogen-activated protein kinase phosphatase (MKP)-1 in immunology, physiology, and disease.
复制标题
DOI：
10.1016/j.lfs.2011.11.017
复制
发表时间：
2012-02-13
期刊：
影响因子：
6.1
通讯作者：
Liu, Yusen
中科院分区：
文献类型：
--
作者：
Wancket, Lyn M.;Frazier, W. Joshua;Liu, Yusen
丝裂原活化蛋白激酶（MAPK）是细胞生理和免疫反应的关键调节因子，MAPKs异常与许多疾病有关。MAPK通过保守的Thr-Xaa-Tyr结构域中的苏氨酸和酪氨酸残基的磷酸化被MAPK激酶激活，其中Xaa代表不同MAPK亚家族的特征性氨基酸残基。由于MAPKs在各种细胞过程中起着至关重要的作用，因此已经进化出一个微妙的调控网络来控制它们的活动。在过去的二十年中，已经鉴定了一组使MAPK失活的双特异性MAPK磷酸酶（MKPs）。由于MAPK可以增强MKP活性，因此MKP被认为是限制MAPK级联反应的重要反馈控制机制。本文综述了MKP-1，一个典型的MKP家族成员，在生理和疾病中的作用。我们将首先讨论MKP-1的基本生物化学和调节。接下来，我们将介绍目前关于MKP-1在感染性、炎症性、代谢性和神经系统疾病中的免疫和生理功能的共识，这些功能是通过使用动物模型的研究揭示的。我们还将讨论新出现的证据表明MKP-1与人类疾病有关。最后，我们将结束与潜在的MKP-1表达的药物调节的讨论。
Mitogen-activated protein kinases (MAPKs) are key regulators of cellular physiology and immune responses and abnormality in MAPKs is implicated in many diseases. MAPKs are activated by MAPK kinases through phosphorylation of the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr domain, where Xaa represents amino acid residues characteristic of distinct MAPK subfamilies. Since MAPKs play a crucial role in a variety of cellular processes, a delicate regulatory network has evolved to control their activities. Over the past two decades, a group of dual specificity MAPK phosphatases (MKPs) have been identified that deactivate MAPKs. Since MAPKs can enhance MKP activities, MKPs are considered as an important feedback control mechanism that limits the MAPK cascades. This review outlines the role of MKP-1, a prototypical MKP family member, in physiology and disease. We will first discuss the basic biochemistry and regulation of MKP-1. Next, we will present the current consensus on the immunological and physiological functions of MKP-1 in infectious, inflammatory, metabolic, and nervous system diseases as revealed by studies using animal models. We will also discuss the emerging evidence implicating MKP-1 in human disorders. Finally, we will conclude with a discussion of the potential for pharmacomodulation of MKP-1 expression.
登录
查看更多内容
DOI：
10.1073/pnas.90.11.5292
发表时间：
1993-06-01
影响因子：
11.1
作者：
CHARLES, CH;SUN, H;TONKS, NK
通讯作者：
TONKS, NK
影响因子：
3.9
作者：
Cho, Il Je;Woo, Na Ri;Kim, Sang Geon
通讯作者：
Kim, Sang Geon
影响因子：
82.9
作者：
Calandra, T;Echtenacher, B;Glauser, MP
通讯作者：
Glauser, MP
影响因子：
3.5
作者：
Arthur, JSC;Cohen, P
通讯作者：
Cohen, P
影响因子：
5.4
作者：
Casals-Casas, Cristina;Alvarez, Eva;Celada, Antonio
通讯作者：
Celada, Antonio