关键词: Diabetes MAP kinase MAP kinase phosphatase Neuropathology Obesity Oncogenic signalling

Mesh : Animals Catalysis Cell Nucleus / metabolism Cytoplasm / metabolism Diabetes Mellitus / metabolism Dual-Specificity Phosphatases / metabolism physiology Humans MAP Kinase Signaling System Mice Mitogen-Activated Protein Kinase Phosphatases / metabolism physiology Mitogen-Activated Protein Kinases / metabolism physiology Neuropathology Obesity / metabolism Phosphoprotein Phosphatases / physiology Phosphorylation Protein Tyrosine Phosphatases / physiology Signal Transduction / physiology Substrate Specificity / physiology

来  源:   DOI:10.1016/j.bbamcr.2018.09.002   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
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.
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