Cited by 285Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingMelanoma and MAPK Pathways

Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions

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Tanoue, Takuji, Maeda, Ryota, Adachi, Makoto, Nishida, Eisuke·2001·The EMBO Journal

Abstract

MAP kinases (MAPKs) form a complex with MAPK kinases (MAPKKs), MAPK-specific phosphatases (MKPs) and various targets including MAPKAPKs. These docking interactions contribute to regulation of the specificity and efficiency of the enzymatic reactions. We have previously identified a docking site on MAPKs, termed the CD (common docking) domain, which is utilized commonly for docking interactions with MAPKKs, MKPs and MAPKAPKs. However, the CD domain alone does not determine the docking specificity. Here we have identified a novel site on p38 and ERK2 MAPKs that regulates the docking specificity towards MAPKAPKs. Remarkably, exchange of two amino acids in this site of ERK2 for corresponding residues of p38 converted the docking specificity for MAPKAPK-3/3pk, which is a dominant target of p38, from the ERK2 type to the p38 type, and vice versa. Furthermore, our detailed analyses with a number of MAPKAPKs and MKPs suggest that a groove in the steric structure of MAPKs, which comprises the CD domain and the site identified here, serves as a common docking region for various MAPK-interacting molecules.

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Crossref · 10.1093/emboj/20.3.466

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Authors
Tanoue, T., Maeda, R., Adachi, M., & Nishida, E.
Affiliations
Kyoto University (JP)
Corresponding author
Nishida, Eisuke
Venue
The EMBO Journal
Published
2001-02-01
Volume
20
Issue
3
Pages
466-479
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2061699263
Cited by
285
References
55
Citations by year
2026: 4 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 8 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 11 · 2014: 6 · 2013: 8 · 2012: 13
FWCI
9.89
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • 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
Keywords
ERK2, p38 MAPK, MAPKAPK2, MAPKAPK
MeSH terms
Amino Acid Sequence, Animals, Binding Sites, Enzyme Activation, Humans, Models, Molecular, Molecular Sequence Data, Protein Conformation, Mutagenesis, 3T3 Cells, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Macromolecular Substances, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Mice, In Vitro Techniques

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