Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module

Gábor Glatz, Gergo Gógl, Anita Alexa, Attila Reményi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Mitogen-activated protein kinase (MAPK) activation depends on a linear binding motif found in all MAPK kinases (MKK). In addition, the PB1 (Phox and Bem1) domain of MKK5 is required for extracellular signal regulated kinase 5 (ERK5) activation. We present the crystal structure of ERK5 in complex with an MKK5 construct comprised of the PB1 domain and the linear binding motif. We show that ERK5 has distinct protein-protein interaction surfaces compared with ERK2, which is the closest ERK5 paralog. The two MAPKs have characteristically different physiological functions and their distinct protein- protein interaction surface topography enables them to bind different sets of activators and substrates. Structural and biochemical characterization revealed that the MKK5 PB1 domain cooperates with the MAPK binding linear motif to achieve substrate specific binding, and it also enables co-recruitment of the upstream activating enzyme and the downstream substrate into one signaling competent complex. Studies on present day MAPKs and MKKs hint on the way protein kinase networks may evolve. In particular, they suggest how paralogous enzymes with similar catalytic properties could acquire novel signaling roles by merely changing the way they make physical links to other proteins.

Original languageEnglish
Pages (from-to)8596-8609
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number12
DOIs
Publication statusPublished - Mar 22 2013

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Mitogen-Activated Protein Kinase 7
Chemical activation
Mitogen-Activated Protein Kinases
Membrane Proteins
Proteins
Substrates
Mitogen-Activated Protein Kinase Kinases
Enzymes
Protein Binding
Protein Kinases
Surface topography
Crystal structure
4-ethoxymethylene-2-phenyl-2-oxazoline-5-one

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module. / Glatz, Gábor; Gógl, Gergo; Alexa, Anita; Reményi, Attila.

In: Journal of Biological Chemistry, Vol. 288, No. 12, 22.03.2013, p. 8596-8609.

Research output: Contribution to journalArticle

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