Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation

Andrei V. Khokhlatchev, Bertram Canagarajah, Julie Wilsbacher, Megan Robinson, Mark Atkinson, Elizabeth Goldsmith, Melanie H. Cobb

Research output: Contribution to journalArticle

538 Citations (Scopus)

Abstract

The MAP kinase ERK2 is widely involved in eukaryotic signal transduction. Upon activation it translocates to the nucleus of the stimulated cell, where it phosphorylates nuclear targets. We find that nuclear accumulation of microinjected ERK2 depends on its phosphorylation state rather than on its activity or on upstream components of its signaling pathway. Phosphorylated ERK2 forms dimers with phosphorylated and unphosphorylated ERK2 partners. Disruption of dimerization by mutagenesis of ERK2 reduces its ability to accumulate in the nucleus, suggesting that dimerization is essential for its normal ligand-dependent relocalization. The crystal structure of phosphorylated ERK2 reveals the basis for dimerization. Other MAP kinase family members also form dimers. The generality of this behavior suggests that dimerization is part of the mechanism of action of the MAP kinase family.

Original languageEnglish (US)
Pages (from-to)605-615
Number of pages11
JournalCell
Volume93
Issue number4
DOIs
StatePublished - May 15 1998

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Phosphorylation
Dimerization
Phosphotransferases
Dimers
Signal transduction
Mutagenesis
Aptitude
Cell Nucleus
Signal Transduction
Crystal structure
Chemical activation
Ligands

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation. / Khokhlatchev, Andrei V.; Canagarajah, Bertram; Wilsbacher, Julie; Robinson, Megan; Atkinson, Mark; Goldsmith, Elizabeth; Cobb, Melanie H.

In: Cell, Vol. 93, No. 4, 15.05.1998, p. 605-615.

Research output: Contribution to journalArticle

Khokhlatchev, AV, Canagarajah, B, Wilsbacher, J, Robinson, M, Atkinson, M, Goldsmith, E & Cobb, MH 1998, 'Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation', Cell, vol. 93, no. 4, pp. 605-615. https://doi.org/10.1016/S0092-8674(00)81189-7
Khokhlatchev AV, Canagarajah B, Wilsbacher J, Robinson M, Atkinson M, Goldsmith E et al. Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation. Cell. 1998 May 15;93(4):605-615. https://doi.org/10.1016/S0092-8674(00)81189-7
Khokhlatchev, Andrei V. ; Canagarajah, Bertram ; Wilsbacher, Julie ; Robinson, Megan ; Atkinson, Mark ; Goldsmith, Elizabeth ; Cobb, Melanie H. / Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation. In: Cell. 1998 ; Vol. 93, No. 4. pp. 605-615.
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