Activation mechanism of the MAP kinase ERK2 by dual phosphorylation

Cell. 1997 Sep 5;90(5):859-69. doi: 10.1016/s0092-8674(00)80351-7.

Abstract

The structure of the active form of the MAP kinase ERK2 has been solved, phosphorylated on a threonine and a tyrosine residue within the phosphorylation lip. The lip is refolded, bringing the phosphothreonine and phosphotyrosine into alignment with surface arginine-rich binding sites. Conformational changes occur in the lip and neighboring structures, including the P+1 site, the MAP kinase insertion, the C-terminal extension, and helix C. Domain rotation and remodeling of the proline-directed P+1 specificity pocket account for the activation. The conformation of the P+1 pocket is similar to a second proline-directed kinase, CDK2-CyclinA, thus permitting the origin of this specificity to be defined. Conformational changes outside the lip provide loci at which the state of phosphorylation can be felt by other cellular components.

Publication types

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

MeSH terms

  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases / chemistry*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Crystallography
  • Dimerization
  • Enzyme Activation
  • Mitogen-Activated Protein Kinase 1
  • Molecular Sequence Data
  • Phosphorylation
  • Proline / chemistry
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Substrate Specificity
  • Threonine / metabolism
  • Tyrosine / metabolism

Substances

  • Threonine
  • Tyrosine
  • Proline
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1

Associated data

  • PDB/2ERK