Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, 35053, Taiwan.
Cell Biosci. 2012 Jul 9;2(1):24. doi: 10.1186/2045-3701-2-24.
Phosphatases are important regulators of intracellular signaling events, and their functions have been implicated in many biological processes. Dual-specificity phosphatases (DUSPs), whose family currently contains 25 members, are phosphatases that can dephosphorylate both tyrosine and serine/threonine residues of their substrates. The archetypical DUSP, DUSP1/MKP1, was initially discovered to regulate the activities of MAP kinases by dephosphorylating the TXY motif in the kinase domain. However, although DUSPs were discovered more than a decade ago, only in the past few years have their various functions begun to be described. DUSPs can be categorized based on the presence or absence of a MAP kinase-interacting domain into typical DUSPs and atypical DUSPs, respectively. In this review, we discuss the current understanding of how the activities of typical DUSPs are regulated and how typical DUSPs can regulate the functions of their targets. We also summarize recent findings from several in vivo DUSP-deficient mouse models that studied the involvement of DUSPs during the development and functioning of T cells. Finally, we discuss briefly the potential roles of DUSPs in the regulation of non-MAP kinase targets, as well as in the modulation of tumorigenesis.
磷酸酶是细胞内信号事件的重要调节因子，其功能涉及许多生物学过程。双特异性磷酸酶（DUSPs）是一类能够去磷酸化其底物的酪氨酸和丝氨酸/苏氨酸残基的磷酸酶，目前其家族包含 25 个成员。原型 DUSP，DUSP1/MKP1，最初被发现通过去磷酸化激酶结构域中的 TXY 基序来调节 MAP 激酶的活性。然而，尽管 DUSPs 早在十多年前就被发现，但直到最近几年，它们的各种功能才开始被描述。根据是否存在 MAP 激酶相互作用域，DUSPs 可分别归类为典型 DUSPs 和非典型 DUSPs。在这篇综述中，我们讨论了目前对典型 DUSPs 活性如何被调节以及典型 DUSPs 如何调节其靶标功能的理解。我们还总结了近年来几个 DUSP 缺陷小鼠模型的研究结果，这些研究探讨了 DUSPs 在 T 细胞发育和功能中的作用。最后，我们简要讨论了 DUSPs 在调节非 MAP 激酶靶标以及调节肿瘤发生中的潜在作用。
