Activation of the MAP kinase pathway by the protein kinase raf

Cell. 1992 Oct 16;71(2):335-42. doi: 10.1016/0092-8674(92)90361-f.


Both MAP kinases and the protein kinase p74raf-1 are activated by many growth factors in a c-ras-dependent manner and by oncogenic p21ras. We were therefore interested in determining the relationship between MAP kinases and raf. The MAP kinase ERK2 is activated by expression of oncogenically activated raf, independently of cellular ras. Overexpressed p74raf-1 potentiates activation of ERK2 by EGF and TPA. MAP kinase kinase inactivated by phosphatase 2A treatment is phosphorylated and reactivated by incubation with p74raf-1 immunoprecipitated from phorbol ester-treated cells. We conclude that raf protein kinase is upstream of MAP kinases and is either a MAP kinase kinase kinase or a MAP kinase kinase kinase kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Enzyme Activation / drug effects
  • Epidermal Growth Factor / pharmacology
  • Gene Expression
  • Mitogen-Activated Protein Kinase 1
  • Phorbol Esters / pharmacology
  • Protein Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins c-raf


  • Phorbol Esters
  • Proto-Oncogene Proteins
  • Epidermal Growth Factor
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1