Integrated Science Center, Department of Biology, College of William and Mary, Williamsburg, VA 23185, USA.
Int J Mol Sci. 2021 Jun 28;22(13):6924. doi: 10.3390/ijms22136924.
The pseudophosphatases, atypical members of the protein tyrosine phosphatase family, have emerged as bona fide signaling regulators within the past two decades. Their roles as regulators have led to a renaissance of the pseudophosphatase and pseudoenyme fields, catapulting interest from a mere curiosity to intriguing and relevant proteins to investigate. Pseudophosphatases make up approximately fourteen percent of the phosphatase family, and are conserved throughout evolution. Pseudophosphatases, along with pseudokinases, are important players in physiology and pathophysiology. These atypical members of the protein tyrosine phosphatase and protein tyrosine kinase superfamily, respectively, are rendered catalytically inactive through mutations within their catalytic active signature motif and/or other important domains required for catalysis. This new interest in the pursuit of the relevant functions of these proteins has resulted in an elucidation of their roles in signaling cascades and diseases. There is a rapid accumulation of knowledge of diseases linked to their dysregulation, such as neuropathies and various cancers. This review analyzes the involvement of pseudophosphatases in diseases, highlighting the function of various role(s) of pseudophosphatases involvement in pathologies, and thus providing a platform to strongly consider them as key therapeutic drug targets.
在过去的二十年中,假磷酸酶作为蛋白酪氨酸磷酸酶家族的非典型成员,已成为真正的信号调节因子。它们作为调节剂的作用引发了假磷酸酶和假酶领域的复兴,使人们从仅仅出于好奇转向对有趣且相关的蛋白质进行研究。假磷酸酶约占磷酸酶家族的 14%,并在进化过程中得到了保守。假磷酸酶与假激酶一起,是生理和病理生理学的重要参与者。这些蛋白酪氨酸磷酸酶和蛋白酪氨酸激酶超家族的非典型成员,由于其催化活性特征基序和/或催化所需的其他重要结构域内的突变,导致其催化失活。对这些蛋白质相关功能的研究兴趣的增加,导致了它们在信号级联和疾病中的作用的阐明。与它们的失调相关的疾病知识迅速积累,例如神经病变和各种癌症。本综述分析了假磷酸酶在疾病中的作用,强调了各种假磷酸酶作用在病理学中的功能,从而为将它们强烈视为关键的治疗药物靶点提供了一个平台。