Regulation of MAP kinase signaling modules by scaffold proteins in mammals

Annu Rev Cell Dev Biol. 2003;19:91-118. doi: 10.1146/annurev.cellbio.19.111401.091942.


The mitogen-activated protein kinase (MAPK) group of serine/threonine protein kinases mediates the response of cells to many extracellular stimuli such as cytokines and growth factors. These protein kinases include the extracellular signal-regulated protein kinases (ERK) and two stress-activated protein kinases (SAPK), the c-Jun N-terminal kinases (JNK), and the p38 MAPK. The enzymes are evolutionarily conserved and are activated by a common mechanism that involves a protein kinase cascade. Scaffold proteins have been proposed to interact with MAPK pathway components to create a functional signaling module and to control the specificity of signal transduction. Here we critically evaluate the evidence that supports a physiologically relevant role of MAPK scaffold proteins in mammals.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Arrestins / metabolism
  • Carrier Proteins / metabolism*
  • Contractile Proteins / metabolism
  • Dual-Specificity Phosphatases
  • Filamins
  • Humans
  • MAP Kinase Kinase Kinase 1*
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System / physiology*
  • Mammals / metabolism
  • Microfilament Proteins / metabolism
  • Phosphoprotein Phosphatases
  • Protein Kinases / metabolism
  • Protein Tyrosine Phosphatases / metabolism
  • beta-Arrestins


  • Adaptor Proteins, Signal Transducing
  • Arrestins
  • Carrier Proteins
  • Contractile Proteins
  • Filamins
  • LAMTOR3 protein, human
  • MAPK8IP1 protein, human
  • Mapk8ip protein, mouse
  • Microfilament Proteins
  • beta-Arrestins
  • Protein Kinases
  • KSR-1 protein kinase
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase Kinases
  • MAP3K1 protein, human
  • Map3k1 protein, mouse
  • Phosphoprotein Phosphatases
  • DUSP7 protein, human
  • Dual-Specificity Phosphatases
  • Protein Tyrosine Phosphatases