Cited by 285Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysMass Spectrometry Techniques and Applications

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.

Docking Motif Interactions in MAP Kinases Revealed by Hydrogen Exchange Mass Spectrometry

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Abstract

Protein interactions between MAP kinases and substrates, activators, and scaffolding proteins are regulated by docking site motifs, one containing basic residues proximal to Leu-X-Leu (DEJL) and a second containing Phe-X-Phe (DEF). Hydrogen exchange mass spectrometry was used to identify regions in MAP kinases protected from solvent by docking motif interactions. Protection by DEJL peptide binding was observed in loops spanning beta7-beta8 and alphaD-alphaE in p38alpha and ERK2. In contrast, protection by DEF binding to ERK2 revealed a distinct hydrophobic pocket for Phe-X-Phe binding formed between the P+1 site, alphaF helix, and the MAP kinase insert. In inactive ERK2, this pocket is occluded by intramolecular interactions with residues in the activation lip. In vitro assays confirm the dependence of Elk1 and nucleoporin binding on ERK2 phosphorylation, and provide a structural basis for preferential involvement of active ERK in substrate binding and nuclear pore protein interactions.

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Crossref · 10.1016/s1097-2765(04)00161-3

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Metadata

Authors
Lee, T., Hoofnagle, A. N., Kabuyama, Y., Stroud, J., Min, X., Goldsmith, E. J., Chen, L., Resing, K. A., & Ahn, N. G.
Affiliations
  • University of Colorado Boulder (US)
  • Howard Hughes Medical Institute (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Ahn, Natalie G
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2004-04
Volume
14
Issue
1
Pages
43-55
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2020513008
Cited by
282
References
35
Citations by year
2026: 3 · 2025: 6 · 2024: 5 · 2023: 12 · 2022: 8 · 2021: 8 · 2020: 11 · 2019: 9 · 2018: 10 · 2017: 11 · 2016: 17 · 2015: 14 · 2014: 9 · 2013: 9 · 2012: 15
FWCI
9.02
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM064642, R01-GM48521, R01GM048521)
  • National Institute of Allergy and Infectious Diseases (R21AI049905)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Keywords
mitogen-activated protein kinase, p38α, ERK2, protein-protein interaction, hydrogen-deuterium exchange mass spectrometry, substrate binding, Elk-1, nucleoporins, activation loop
MeSH terms
Amino Acid Sequence, Animals, Binding Sites, Enzyme Activation, Models, Molecular, Molecular Sequence Data, Mutation, Peptides, Protein Binding, Mass Spectrometry, Sequence Alignment, Protein Structure, Tertiary, Mitogen-Activated Protein Kinases, Rats

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