Dual-specificity MAP kinase phosphatases in health and disease

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1866; no. 1; pp. 124 - 143
• Main Authors: Seternes, Ole-Morten, Kidger, Andrew M., Keyse, Stephen M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019; Elsevier
• Subjects: Animals; Basale medisinske, odontologiske og veterinærmedisinske fag: 710; Basic medical, dental and veterinary science disciplines: 710; Catalysis; Cell Nucleus - metabolism; Cytoplasm - metabolism; Diabetes; Diabetes Mellitus - metabolism; Dual-Specificity Phosphatases - metabolism; Dual-Specificity Phosphatases - physiology; Humans; MAP kinase; MAP kinase phosphatase; MAP Kinase Signaling System; Medical disciplines: 700; Medical molecular biology: 711; Medisinsk molekylærbiologi: 711; Medisinske Fag: 700; Mice; Mitogen-Activated Protein Kinase Phosphatases - metabolism; Mitogen-Activated Protein Kinase Phosphatases - physiology; Mitogen-Activated Protein Kinases - metabolism; Mitogen-Activated Protein Kinases - physiology; Neuropathology; Obesity; Obesity - metabolism; Oncogenic signalling; Phosphoprotein Phosphatases - physiology; Phosphorylation; Protein Tyrosine Phosphatases - physiology; Signal Transduction - physiology; Substrate Specificity - physiology; VDP; MAP kinase phosphatase; Obesity; Oncogenic signalling; MAP kinase; Diabetes; Neuropathology
• ISSN: 0167-4889; 1879-2596; 1879-2596
• DOI: 10.1016/j.bbamcr.2018.09.002

It is well established that a family of dual-specificity MAP kinase phosphatases (MKPs) play key roles in the regulated dephosphorylation and inactivation of MAP kinase isoforms in mammalian cells and tissues. MKPs provide a mechanism of spatiotemporal feedback control of these key signalling pathways, but can also mediate crosstalk between distinct MAP kinase cascades and facilitate interactions between MAP kinase pathways and other key signalling modules. As our knowledge of the regulation, substrate specificity and catalytic mechanisms of MKPs has matured, more recent work using genetic models has revealed key physiological functions for MKPs and also uncovered potentially important roles in regulating the pathophysiological outcome of signalling with relevance to human diseases. These include cancer, diabetes, inflammatory and neurodegenerative disorders. It is hoped that this understanding will reveal novel therapeutic targets and biomarkers for disease, thus contributing to more effective diagnosis and treatment for these debilitating and often fatal conditions. •A comprehensive review of the dual-specificity MAP kinase Phosphatases (MKPs)•Focus is on MKPs in the regulation of MAPK signalling in health and disease.•Covers roles of MKPs in inflammation, obesity/diabetes, cancer and neurodegeneration