The Mitogen Activated Protein Kinase Signal Transduction Pathway: From the Cell Surface to the Nucleus

Cell Signal. 1994 Aug;6(6):581-9. doi: 10.1016/0898-6568(94)90041-8.


Activation of the mitogen activated protein kinase (MAPK) plays essential roles in many signal transduction pathways. MAPK has been demonstrated to phosphorylate and regulate numerous cellular proteins, including growth factor receptor, transcription factors, cytoskeletal proteins, phospholipase and other protein kinases. Activation of MAPK requires phosphorylation of both threonine and tyrosine residues, which are catalysed by a single protein kinase known as MAPK kinase or MEK. MEK itself is activated by phosphorylation on two conserved serine residues. Three distinct mammalian Ser/Thr kinases, including Raf, Mos and MEKK (for MEK kinase), have been demonstrated to phosphorylate and activate MEK. The MAP kinase cascade is highly conserved in all eukaryotes and involved in numerous cellular responses. Activation of MAPK is a transient event that is tightly regulated by both kinases and phosphatases. A growth factor induced dual specific phosphatase is likely to play an important role in MAPK regulation.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / physiology
  • Cell Nucleus / physiology
  • Enzyme Activation
  • Humans
  • MAP Kinase Kinase 2
  • MAP Kinase Kinase Kinase 1*
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase Kinases*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / physiology*
  • Protein-Tyrosine Kinases / physiology*
  • Signal Transduction / physiology*


  • MAP2K2 protein, human
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • MAP Kinase Kinase 2
  • Mitogen-Activated Protein Kinase Kinases