Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
Institute of Evolution & Marine Biodiversity, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China.
Cell Commun Signal. 2017 Sep 20;15(1):35. doi: 10.1186/s12964-017-0191-0.
Hedgehog signaling is evolutionarily conserved and plays a pivotal role in cell fate determination, embryonic development, and tissue renewal. As aberrant Hedgehog signaling is tightly associated with a broad range of human diseases, its activities must be precisely controlled. It has been known that several core components of Hedgehog pathway undergo reversible phosphorylations mediated by protein kinases and phosphatases, which acts as an effective regulatory mechanism to modulate Hedgehog signal activities. In contrast to kinases that have been extensively studied in these phosphorylation events, phosphatases were thought to function in an unspecific manner, thus obtained much less emphasis in the past. However, in recent years, increasing evidence has implicated that phosphatases play crucial and specific roles in the context of developmental signaling, including Hedgehog signaling. In this review, we present a summary of current progress on phosphatase studies in Hedgehog pathway, emphasizing the multiple employments of protein serine/threonine phosphatases during the transduction of morphogenic Hedgehog signal in both Drosophila and vertebrate systems, all of which provide insights into the importance of phosphatases in the specific regulation of Hedgehog signaling.
Hedgehog 信号通路在进化上具有保守性，在细胞命运决定、胚胎发育和组织更新中发挥着关键作用。由于异常的 Hedgehog 信号与广泛的人类疾病密切相关，因此必须对其活性进行精确控制。已知 Hedgehog 途径的几个核心成分可通过蛋白激酶和磷酸酶介导的可逆磷酸化作用，这是一种有效的调节机制，可调节 Hedgehog 信号活性。与在这些磷酸化事件中得到广泛研究的激酶不同，磷酸酶被认为以非特异性方式发挥作用，因此在过去受到的关注较少。然而，近年来，越来越多的证据表明，磷酸酶在发育信号转导中（包括 Hedgehog 信号转导）发挥着至关重要和特异性的作用。在这篇综述中，我们总结了 Hedgehog 途径中磷酸酶研究的最新进展，强调了蛋白丝氨酸/苏氨酸磷酸酶在果蝇和脊椎动物系统中形态发生性 Hedgehog 信号转导中的多种应用，所有这些都为磷酸酶在 Hedgehog 信号的特异性调节中的重要性提供了新的见解。
