Pulido Rafael, Hooft van Huijsduijnen Rob
Centro de Investigación Príncipe Felipe, Valencia, Spain.
FEBS J. 2008 Mar;275(5):848-66. doi: 10.1111/j.1742-4658.2008.06250.x.
Dual-specificity phosphatases (DSPs) constitute a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylates phospho-Tyr, phospho-Ser and nonproteinaceous substrates. DSPs are involved in the regulation of both developmental and postnatal essential processes, such as early embryogenesis, placental development and immune responses. Several DSP genes are implicated in familial and sporadic human diseases, including tumor-related, neurological and muscle disorders, and cardiovascular and inflammatory diseases. This association ranges from disease-causative mutations to disease-risk-prone single-nucleotide polymorphisms, promoter methylation or gene duplication (most often in cancer). Deconvolution of the role of DSPs in disease is challenging. The enzymes' activities are regulated at many levels and they form part of extensive, intricate networks with other signaling components. Here, we review current knowledge of the role of cysteine-based PTP-domain DSPs in health and disease, and their suitability as putative therapeutic targets for drugs is discussed.
双特异性磷酸酶（DSPs）构成了蛋白质酪氨酸磷酸酶（PTPs）的一个亚家族，可使磷酸化酪氨酸、磷酸化丝氨酸和非蛋白质底物去磷酸化。DSPs参与发育和出生后基本过程的调节，如早期胚胎发生、胎盘发育和免疫反应。几个DSP基因与家族性和散发性人类疾病有关，包括肿瘤相关疾病、神经和肌肉疾病以及心血管和炎症性疾病。这种关联范围从致病突变到疾病易感性单核苷酸多态性、启动子甲基化或基因复制（最常见于癌症）。解析DSPs在疾病中的作用具有挑战性。这些酶的活性在多个水平上受到调节，并且它们与其他信号成分构成广泛而复杂的网络的一部分。在这里，我们综述了基于半胱氨酸的PTP结构域DSPs在健康和疾病中的作用的当前知识，并讨论了它们作为药物潜在治疗靶点的适用性。
