Dual-specificity MAP kinase phosphatases in health and disease

Ole-Morten Seternes, Andrew M. Kidger, Stephen Keyse (Lead / Corresponding author)

Research output: Contribution to journalArticle

13 Citations (Scopus)
188 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)124-143
Number of pages20
JournalBBA - Molecular Cell Research
Volume1866
Issue number1
Early online date8 Sep 2018
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

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

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