Untying the regulation of the Raf-1 kinase

Arch Biochem Biophys. 2002 Aug 1;404(1):3-9. doi: 10.1016/s0003-9861(02)00244-8.


The Raf-1 kinase is the entry point to the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK-1/2) signaling pathway, which controls fundamental cellular functions including proliferation, differentiation, and survival. As such, Raf-1 is regulated by complex mechanisms that are incompletely understood. Recent results have shown that release from repression is an important event that facilitates the interaction of Raf-1 with the Ras activator and its substrate, MAPK/ERK-1/2 kinase. A number of distinct activation steps contribute in a combinatorial fashion to regulate and adjust Raf-1 activity. The efficiency of downstream signal transmission is modulated by protein:protein interactions, and new data consolidate an important role for kinase suppressor of ras (KSR) as a scaffolding protein. KSR is a dynamic scaffold whose function and localization is regulated by phosphorylation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclic AMP / metabolism
  • Enzyme Activation
  • Lipid Metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Phosphorylation
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Signal Transduction
  • ras Proteins / metabolism


  • Cyclic AMP
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • ras Proteins