Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells

Cell. 1994 Jun 17;77(6):841-52. doi: 10.1016/0092-8674(94)90133-3.


The MAP kinase pathway is activated by a wide variety of external signals leading to cell proliferation or differentiation. However, it is not clear whether activation of this pathway is required for cellular responses or whether it is only one branch point in signal transduction. To investigate these questions, we generated constitutively activated and interfering mutants of MAP kinase kinase 1. The activated mutants stimulated PC12 cell neuronal differentiation and transformed NIH 3T3 cells. The interfering mutants inhibited growth factor-induced PC12 differentiation, growth factor stimulation of proliferation, and reverted v-src- and ras-transformed cells. These results therefore show that, depending on cellular context, activation of MAP kinase kinase is necessary and sufficient for cell differentiation or proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alanine / metabolism
  • Animals
  • Cell Differentiation*
  • Cell Division
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Culture Media, Serum-Free
  • DNA / biosynthesis
  • Enzyme Activation
  • Glutamates / metabolism
  • Glutamic Acid
  • Mice
  • Mitogen-Activated Protein Kinase Kinases
  • Mutation
  • Neurites / ultrastructure
  • Neurons / cytology*
  • Neurons / enzymology
  • Neurons / ultrastructure
  • PC12 Cells
  • Protein Kinase Inhibitors
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Serine / metabolism
  • Signal Transduction


  • Culture Media, Serum-Free
  • Glutamates
  • Protein Kinase Inhibitors
  • Glutamic Acid
  • Serine
  • DNA
  • Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Alanine