Creation of a stress-activated p90 ribosomal S6 kinase. The carboxyl-terminal tail of the MAPK-activated protein kinases dictates the signal transduction pathway in which they function

J Biol Chem. 2000 Oct 13;275(41):31588-93. doi: 10.1074/jbc.M005892200.

Abstract

Mitogen-activated protein kinase-activated protein kinases (MAPKAPKs) lie immediately downstream of the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), and p38 MAPK. Although the family of MAPKAPKs shares sequence similarity, it demonstrates selectivity for the upstream activator. Here we demonstrate that each of the ERK- and p38 MAPK-regulated MAPKAPKs contains a MAPK docking site positioned distally to the residue(s) phosphorylated by MAPKs. The isolated MAPK docking sites show specificity for the upstream activator similar to that reported for the full-length proteins. Moreover, replacement of the ERK docking site of p90 ribosomal S6 kinase with the p38 MAPK docking site of MAPKAPK2 converts p90 ribosomal S6 kinase into a stress-activated kinase in vivo. It is apparent that mechanisms controlling events downstream of the proline-directed MAPKs involve specific MAPK docking sites within the carboxyl termini of the MAPKAPKs that determine the cascade in which the MAPKAPK functions.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Cricetinae
  • Enzyme Activation
  • Humans
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinase Kinases / chemistry
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / chemistry
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • Phosphorylation
  • Precipitin Tests
  • Protein Engineering*
  • Protein Structure, Tertiary
  • Rats
  • Receptors, Estrogen / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribosomal Protein S6 Kinases / chemistry
  • Ribosomal Protein S6 Kinases / genetics
  • Ribosomal Protein S6 Kinases / metabolism*
  • Substrate Specificity
  • Transfection
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Ribosomal Protein S6 Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases