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Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase
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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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“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).”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [37]
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A Toolbox of Structural Biology and Enzyme Kinetics Reveals the Case for ERK Docking Site Inhibition
Sammons, R. M., & Dalby, K. N. (2020) · Springer eBooks · doi:10.1007/978-3-030-48283-1_6 · Cited by 3
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Nfya-1 functions as a substrate of ERK-MAP kinase during Caenorhabditis elegans vulval development
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MAPK Kinase Kinase Regulation of SAPK/JNK Pathways
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Metadata
- Authors
- Jacobs, D., Glossip, D., Xing, H., Muslin, A. J., & Kornfeld, K.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- 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
- bronze
- doi.org
- 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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