Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase

Dave Jacobs, Danielle Glossip, Heming Xing, Anthony J. Muslin, Kerry Kornfeld

Research output: Contribution to journalArticlepeer-review

431 Scopus citations

Abstract

MAP kinases phosphorylate specific groups of substrate proteins. Here we show that the amino acid sequence FXFP is an evolutionarily conserved docking site that mediates ERK MAP kinase binding to substrates in multiple protein families. FXFP and the D box, a different docking site, form a modular recognition system, as they can function independently or in combination. FXFP is specific for ERK, whereas the D box mediates binding to ERK and JNK MAP kinase, suggesting that the partially overlapping substrate specificities of ERK and JNK result from recognition of shared and unique docking sites. These findings enabled us to predict new ERK substrates and design peptide inhibitors of ERK that functioned in vitro and in vivo.

Original languageEnglish
Pages (from-to)163-175
Number of pages13
JournalGenes and Development
Volume13
Issue number2
DOIs
StatePublished - Jan 15 1999

Keywords

  • ERK
  • ETS transcription factor
  • JNK
  • KSR
  • MAP kinase

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