The MEK/ERK cascade: from signaling specificity to diverse functions

Biochim Biophys Acta. 2007 Aug;1773(8):1213-26. doi: 10.1016/j.bbamcr.2006.10.005. Epub 2006 Oct 19.


The ERK signaling cascade is a central MAPK pathway that plays a role in the regulation of various cellular processes such as proliferation, differentiation, development, learning, survival and, under some conditions, also apoptosis. The ability of this cascade to regulate so many distinct, and even opposing, cellular processes, raises the question of signaling specificity determination by this cascade. Here we describe mechanisms that cooperate to direct MEK-ERK signals to their appropriate downstream destinations. These include duration and strength of the signals, interaction with specific scaffolds, changes in subcellular localization, crosstalk with other signaling pathways, and presence of multiple components with distinct functions in each tier of the cascade. Since many of the mechanisms do not function properly in cancer cells, understanding them may shed light not only on the regulation of normal cell proliferation, but also on mechanisms of oncogenic transformation.

Publication types

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

MeSH terms

  • Animals
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / physiology
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology*
  • Models, Biological
  • Multiprotein Complexes
  • Mutation
  • Phosphorylation
  • Subcellular Fractions / enzymology


  • Isoenzymes
  • Multiprotein Complexes
  • Extracellular Signal-Regulated MAP Kinases