Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases

J Biol Chem. 1993 Nov 15;268(32):23933-9.


Activation of extracellular signal-regulated kinase (ERK) or mitogen-activated protein kinase by MEK (mitogen-activated protein kinase or extracellular signal-regulated kinase kinase) is an essential event in the mitogenic growth factor signal transduction. We now demonstrate that three recombinant MEKs (MEK1, MEK2, MEK3) show remarkably different activity toward recombinant ERK1 and ERK2. MEK2 is the most active ERK activator. The recombinant MEK1 has an activity approximately seven times lower than that of MEK2. MEK3, which is identical to MEK1 except for missing an internal 26-amino acid residue and probably represents an alternative splicing product of MEK1, shows neither autophosphorylation nor ERK-activating activity. Recombinant MEK1 and MEK2 can be activated by epidermal growth factor-stimulated SWISS3T3 cell lysate. MEK1 and MEK2 can also be activated by autophosphorylation. Autophosphorylation of MEKs correlates with their ability to phosphorylate and activate ERKs. Phosphorylation of MEK is also stimulated by ERK. Phosphoamino acid analysis showed that ERK1 preferentially phosphorylated threonine residue of MEKs. MEKs complex with ERKs in vitro. Interestingly, MEK3 also forms a complex with ERK1, although it is totally inactive as an ERK activator.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / isolation & purification
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Chromatography, Liquid
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Humans
  • MAP Kinase Kinase 1
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Serine-Threonine Kinases*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / isolation & purification
  • Protein-Tyrosine Kinases / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Signal Transduction*


  • DNA Primers
  • Recombinant Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases