Protein scaffolds in MAP kinase signalling

Cell Signal. 2009 Apr;21(4):462-9. doi: 10.1016/j.cellsig.2008.11.013. Epub 2008 Dec 3.


The mitogen-activated protein kinase (MAPK) pathway allows cells to interpret external signals and respond in an appropriate way. Diverse cellular functions, ranging from differentiation and proliferation to migration and inflammation, are regulated by MAPK signalling. Therefore, cells have developed mechanisms by which this single pathway modulates numerous cellular responses from a wide range of activating factors. This specificity is achieved by several mechanisms, including temporal and spatial control of MAPK signalling components. Key to this control are protein scaffolds, which are multidomain proteins that interact with components of the MAPK cascade in order to assemble signalling complexes. Studies conducted on different scaffolds, in different biological systems, have shown that scaffolds exert substantial control over MAPK signalling, influencing the signal intensity, time course and, importantly, the cellular responses. Protein scaffolds, therefore, are integral elements to the modulation of the MAPK network in fundamental physiological processes.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Arrestins / physiology
  • Cell Compartmentation
  • Drug Delivery Systems
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Humans
  • MAP Kinase Kinase 4 / physiology
  • MAP Kinase Kinase Kinases / physiology
  • MAP Kinase Signaling System / physiology*
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / physiology
  • Protein Kinases / physiology
  • Receptors, Interleukin / physiology
  • Substrate Specificity
  • beta-Arrestins
  • p38 Mitogen-Activated Protein Kinases / physiology
  • ras GTPase-Activating Proteins / physiology


  • Adaptor Proteins, Signal Transducing
  • Arrestins
  • IL17RD protein, human
  • IQ motif containing GTPase activating protein 1
  • LAMTOR3 protein, human
  • Multiprotein Complexes
  • Receptors, Interleukin
  • beta-Arrestins
  • ras GTPase-Activating Proteins
  • Protein Kinases
  • KSR-1 protein kinase
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP Kinase Kinase 4