Cited by 440Melanoma and MAPK PathwaysProtein Kinase Regulation and GTPase SignalingProtein Tyrosine Phosphatases

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

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Jacobs, D., Glossip, D., Xing, H., Muslin, A. J., Kornfeld, K.·1999·Genes & Development

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.

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Crossref · 10.1101/gad.13.2.163

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  • FxFP motifs in certain MAPK substrates and a separate docking groove for such motifs on ERK suggest that two docking grooves on ERK may operate in combination; Elk1 contains both an FxFP and a D-motif.

    “Moreover, the existence of FxFP (Phe-any amino acid-Phe-Pro) motifs in certain MAPK (especially ERK) substrates and a separate docking groove for such motifs on ERK suggest that in some cases two docking grooves on ERK may operate in combination: Elk1 for example contains both an FxFP and a D-motif (35-37).”

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Authors
Jacobs, D., Glossip, D., Xing, H., Muslin, A. J., & Kornfeld, K.
Affiliations
Washington University in St. Louis (US)
Venue
Genes & Development
Published
1999-01-15
Volume
13
Issue
2
Pages
163-175
ISSN
0890-9369 (ISSN-L)
OpenAlex
W4239714346
Cited by
439
References
49
Citations by year
2026: 8 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 16 · 2021: 12 · 2020: 13 · 2019: 7 · 2018: 13 · 2017: 13 · 2016: 16 · 2015: 15 · 2014: 10 · 2013: 13 · 2012: 15
Type
posted content
Language
en
Open access
Locations
Genes & Development (publishedVersion)
Funders
  • Burroughs Wellcome Fund
  • Foundation for Barnes-Jewish Hospital
  • Edward Mallinckrodt, Jr. Foundation
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
ERK MAP kinase, docking site, D-box, substrate specificity, JNK MAP kinase, phosphorylation, peptide inhibitors

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