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Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase.

Mitogen-activated protein/ERK kinase kinases (MEKKs) phosphorylate and activate protein kinases which in turn phosphorylate and activate the p42/44 mitogen-activated protein kinase (MAPK), c-Jun/stress-activated protein kinases (JNKs), and p38/Hog1 kinase. We have isolated the cDNAs for two novel mammalian MEKKs (MEKK 2 and 3). MEKK 2 and 3 encode proteins of 69.7 and 71 kDa, respectively. The kinase domains encoded in the COOH-terminal moiety are 94% conserved; the NH2-terminal moieties are approximately 65% homologous, suggesting this region may encode sequences conferring differential regulation of the two kinases. Expression of MEKK 2 or 3 in HEK293 cells results in activation of p42/44MAPK and JNK but not of p38/Hog1 kinase. Immunoprecipitated MEKK 2 phosphorylated the MAP kinase kinases, MEK 1, and JNK kinase. Titration of MEKK 2 and 3 expression in transfection assays indicated that MEKK 2 preferentially activated JNK while MEKK 3 preferentially activated p42/44MAPK. These findings define a family of MEKK proteins capable of regulating sequential protein kinase pathways involving MAPK members.

Pubmed ID: 8621389


  • Blank JL
  • Gerwins P
  • Elliott EM
  • Sather S
  • Johnson GL


The Journal of biological chemistry

Publication Data

March 8, 1996

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 58157
  • Agency: NIDDK NIH HHS, Id: DK 37871
  • Agency: NIGMS NIH HHS, Id: GM 30324

Mesh Terms

  • Amino Acid Sequence
  • Antibodies
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence
  • DNA Primers
  • DNA, Complementary
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Kinetics
  • MAP Kinase Kinase 2
  • MAP Kinase Kinase 3
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases
  • Molecular Sequence Data
  • Peptide Fragments
  • Phosphorylation
  • Polymerase Chain Reaction
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Recombinant Proteins
  • Sequence Homology, Amino Acid
  • Transfection