Dual-specificity phosphatases: an update on their activity regulation and roles in metabolic diseases

Abstract

Reversible protein phosphorylation is catalyzed by both protein kinases and phosphatases, affecting cellular signal transduction in physiological and pathological processes. In contrast to protein kinases, the substrates and in vivo function of approximately 200 phosphatases are less characterized. The big family of protein phosphatases consists of serine/threonine phosphatases, tyrosine phosphatases, and dual-specificity phosphatases (DUSPs), which dephosphorylate both serine/threonine, and tyrosine residues within the target proteins. Over the last two decades, progress in the study of DUSPs allows for not only a better understanding of their activation and signaling termination but also the effect of their abnormal expression in the development of various diseases, such as diabetes, cancer, neurodegenerative disorders, and nonalcoholic fatty liver disease. The focus of this minireview is to discuss current understanding of transcriptional and post-translational regulation of DUSPs, as well as their emerging roles in energy metabolism.