Activation mechanism of the MAP kinase ERK2 by dual phosphorylation

Bertram J. Canagarajah, Andrei Khokhlatchev, Melanie H. Cobb, Elizabeth J. Goldsmith

Research output: Contribution to journalArticle

580 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)859-869
Number of pages11
JournalCell
Volume90
Issue number5
DOIs
StatePublished - 1997

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Phosphorylation
Lip
Phosphotransferases
Chemical activation
Proline
Phosphothreonine
Phosphotyrosine
Threonine
Tyrosine
Arginine
Conformations
Binding Sites

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Activation mechanism of the MAP kinase ERK2 by dual phosphorylation. / Canagarajah, Bertram J.; Khokhlatchev, Andrei; Cobb, Melanie H.; Goldsmith, Elizabeth J.

In: Cell, Vol. 90, No. 5, 1997, p. 859-869.

Research output: Contribution to journalArticle

Canagarajah, Bertram J. ; Khokhlatchev, Andrei ; Cobb, Melanie H. ; Goldsmith, Elizabeth J. / Activation mechanism of the MAP kinase ERK2 by dual phosphorylation. In: Cell. 1997 ; Vol. 90, No. 5. pp. 859-869.
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