Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions
Open accessAbstract
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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The majority of MAPK regulatory proteins investigated thus far contain KIMs.
“The majority of MAPK regulatory proteins investigated thus far contain KIMs.”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [22]
D-motifs facilitate binding between specific MAPKs and their partner proteins in MAPK signaling networks.
“D-motifs play an important role in MAPK signaling networks by facilitating binding between specific MAPKs and their partner proteins (16, 19-21).”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [19]
The ED-site (also called the MAPK top region) helps determine MAPK-MAPKAPK wiring in cells.
“Similarly, the specificity of ERK2/p38 chimeras had already been tested (19), which showed that the “ED-site” (also known as the MAPK top region) helps to define MAPK-MAPKAPK wiring in cells.”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [19]
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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
- PMC
- PMC133461
- 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
- green
- europepmc.org
- 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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