Institute of Developmental Biology and Cancer, CNRS, UMR 6543, Université Nice-Sophia, Nice, France.
Am J Physiol Cell Physiol. 2010 Aug;299(2):C189-202. doi: 10.1152/ajpcell.00347.2009. Epub 2010 May 12.
Intracellular signaling by mitogen-activated protein (MAP) kinases (MAPK) is involved in many cellular responses and in the regulation of various physiological and pathological conditions. Tight control of the localization and duration of extracellular-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), or p38 MAPK activity is thus a fundamental aspect of cell biology. Several members of the dual-specificity phosphatase (DUSPs) family are able to dephosphorylate MAPK isoforms with different specificity, cellular, and tissue localization. Understanding how these phosphatases are themselves regulated during development or in physiological and pathological conditions is therefore fundamental. Over the years, gene deletion and knockdown studies have completed initial in vitro studies and shed a new light on the global and specific roles of DUSPs in vivo. Whereas DUSP1, DUSP2, and DUSP10 appear as crucial players in the regulation of immune responses, other members of the family, like the ERK-specific DUSP6, were shown to play a major role in development. Recent findings on the involvement of DUSPs in cancer progression and resistance will also be discussed.
丝裂原活化蛋白（MAP）激酶（MAPK）的细胞内信号转导参与许多细胞反应，并调节各种生理和病理状况。因此，严格控制细胞外调节激酶（ERK）、c-Jun NH（2）-末端激酶（JNK）或 p38 MAPK 活性的定位和持续时间是细胞生物学的基本方面。双特异性磷酸酶（DUSPs）家族的几个成员能够以不同的特异性、细胞和组织定位去磷酸化 MAPK 同工型。因此，了解这些磷酸酶本身在发育过程中或在生理和病理条件下是如何被调节的是至关重要的。多年来，基因缺失和敲低研究完成了初步的体外研究，并为 DUSPs 在体内的全局和特定作用提供了新的认识。虽然 DUSP1、DUSP2 和 DUSP10 似乎是调节免疫反应的关键因子，但该家族的其他成员，如 ERK 特异性 DUSP6，则在发育过程中发挥主要作用。还将讨论 DUSPs 在癌症进展和耐药性中的作用的最新发现。
