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Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms.

Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.

Pubmed ID: 7839144


  • DĂ©rijard B
  • Raingeaud J
  • Barrett T
  • Wu IH
  • Han J
  • Ulevitch RJ
  • Davis RJ


Science (New York, N.Y.)

Publication Data

February 3, 1995

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI15136
  • Agency: NCI NIH HHS, Id: CA58396
  • Agency: NIGMS NIH HHS, Id: GM37696

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Cloning, Molecular
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 3
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Signal Transduction
  • Substrate Specificity
  • Transfection
  • p38 Mitogen-Activated Protein Kinases