Components of a new human protein kinase signal transduction pathway

J Biol Chem. 1995 May 26;270(21):12665-9. doi: 10.1074/jbc.270.21.12665.

Abstract

We have identified two components of a new protein kinase signaling cascade, MAPK/ERK kinase 5 (MEK5) and extracellular signal-regulated kinase 5 (ERK5). The MEK5 cDNA was isolated by degenerate PCR and encodes a 444-amino acid protein, which has approximately 40% identity to known MEKs. ERK5 was identified by a specific interaction with the MEK5 mutants S311A/T315A and K195M in the yeast two-hybrid system. The proteins were found to interact in an in vitro binding assay as well. ERK5 did not interact with MEK1 or MEK2. ERK5 is predicted to contain 815 amino acids and is approximately twice the size of all known ERKs. The C terminus of ERK5 has sequences which suggest that it may be targeted to the cytoskeleton. Sequences located in the N terminus of MEK5 may be important in coupling GTPase signaling molecules to the MEK5 protein kinase cascade. Both MEK5 and ERK5 are expressed in many adult tissue and are abundant in heart and skeletal muscle. A recombinant GST-ERK5 kinase domain displays autophosphorylation on Ser/Thr and Tyr residues.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Humans
  • MAP Kinase Kinase 5
  • Mitogen-Activated Protein Kinase 7
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Phosphorylation
  • Polymerase Chain Reaction
  • Protein Binding
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Selection, Genetic
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • Yeasts / genetics

Substances

  • Recombinant Fusion Proteins
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 7
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 5
  • MAP2K5 protein, human
  • Mitogen-Activated Protein Kinase Kinases

Associated data

  • GENBANK/U25265
  • GENBANK/U25278