Identification of a MAP kinase kinase kinase in phaeochromocytoma (PC12) cells

FEBS Lett. 1992 Dec 21;314(3):461-5. doi: 10.1016/0014-5793(92)81527-s.


A MAP kinase kinase kinase (MAPKKK) was identified in phaeochromocytoma (PC12) cells which reactivated homogeneous MAP kinase kinase (MAPKK) from rabbit skeletal muscle that had been inactivated by incubation with protein phosphatase 2A. Reactivation was accompanied by stoichiometric phosphorylation of MAPKK on a serine residue(s). Following stimulation of PC12 cells with nerve growth factor and chromatography of the extracts on Mono Q, MAP kinase and MAPKK were detected as active phosphorylated enzymes, whereas MAPKKK was inactive and only activated after prolonged storage at 4 degrees C. The results suggest that the activation of MAPKKK by growth factors is likely to occur by a non-covalent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Activation
  • Kinetics
  • MAP Kinase Kinase Kinases
  • Mice
  • PC12 Cells
  • Protein Serine-Threonine Kinases / metabolism*
  • Rabbits


  • Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases