Protein phosphatases and the regulation of mitogen-activated protein kinase signalling

Curr Opin Cell Biol. 2000 Apr;12(2):186-92. doi: 10.1016/s0955-0674(99)00075-7.


The magnitude and duration of signalling through mitogen- and stress-activated kinases are critical determinants of biological effect. This reflects a balance between the activities of upstream activators and a complex regulatory network of protein phosphatases. These mitogen-activated protein kinase phosphatases include both dual-specificity (threonine/tyrosine) and tyrosine-specific enzymes, and recent evidence suggests that a single mitogen-activated protein kinase isoform may be acted upon by both classes of protein phosphatase. In both cases, substrate selectivity is determined by specific protein-protein interactions mediated through noncatalytic amino-terminal mitogen-activated protein kinase binding domains. Future challenges include the determination of exactly how this network of protein phosphatases interacts selectively with mitogen-activated protein kinase signalling complexes to achieve precise regulation of these key pathways in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Catalysis
  • Enzyme Activation
  • Humans
  • Isoenzymes / metabolism
  • MAP Kinase Signaling System*
  • Mitogens / pharmacology
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein Tyrosine Phosphatases / physiology
  • Substrate Specificity


  • Isoenzymes
  • Mitogens
  • Protein Tyrosine Phosphatases