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Cited by 119Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingProtein Structure and Dynamics

Solution Structure of ERK2 Binding Domain of MAPK Phosphatase MKP-3

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Farooq, Amjad, Chaturvedi, Gaurav, Mujtaba, Shiraz, Plotnikova, Olga, Zeng, Lei, Dhalluin, Christophe, Ashton, Robert, Zhou, Ming-Ming·2001·Molecular Cell
DOI 10.1016/s1097-2765(01)00186-1
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Abstract

MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal domain binding to the MAPK ERK2, resulting in the activation of its C-terminal phosphatase domain. The solution structure and biochemical analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 binding partly overlap with its sites that interact with the C-terminal catalytic domain, and that these interactions are functionally coupled to the active site residues of MKP-3. Our findings suggest a novel mechanism by which the EB domain binding to ERK2 is transduced to cause a conformational change of the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3.

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Crossref · 10.1016/s1097-2765(01)00186-1

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  • In DUSPs/MKPs, the KIM is not a linear peptide but part of the structured MKBD domain and is much more constrained than that of MKKs or KIM-PTPs.

    “In DUSPs/MKPs, the KIM is not a linear peptide but instead part of the structured MKBD domain [35][36][37] and thus is much more constrained than that of e.g.MKKs or KIM-PTPs.”

    From Molecular basis of MAP kinase regulation (2013) · cites this paper as [36]

  • The MKBDs of DUSP6/MKP3, DUSP10/MKP5, and DUSP16/MKP7 have been structurally characterized.

    “The MKBDs of DUSP6/MKP3 36 (NMR spectroscopy), DUSP10/MKP5 37 (X-ray crystallography) and DUSP16/MKP7 35 (X-ray crystallography) have been structurally characterized.”

    From Molecular basis of MAP kinase regulation (2013) · cites this paper as [36]

  • There are larger structural differences in the MKBD from DUSP6, which also has the central 5-membered β-sheet but the surrounding α-helices and connecting loops adopt significantly different conformations.

    “there are larger structural differences in the MKBD from DUSP6, 36 which also has the central 5-membered b-sheet but the surrounding ahelices and connecting loops adopt significantly different conformations.”

    From Molecular basis of MAP kinase regulation (2013) · cites this paper as [36]

  • The MKBDs of DUSP6/MKP3, DUSP10/MKP5, and DUSP16/MKP7 all adopt a common mixed α/β-fold that is highly similar to that of sulfurtransferases (rhodaneses) and the DUSP Cdc25A.

    “All adopt a common mixed a/b-fold that is highly similar to that of sulfurtransferases (rhodaneses) and the DUSP Cdc25A.”

    From Molecular basis of MAP kinase regulation (2013) · cites this paper as [36]

  • Binding of the MKBD to MAPKs can further activate the phosphatase activity of the DUSP.

    “binding of the MKBD to MAPKs can further activate the phosphatase activity of the DUSP”

    From Molecular basis of MAP kinase regulation (2013) · cites this paper as [36]

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Authors
Farooq, A., Chaturvedi, G., Mujtaba, S., Plotnikova, O., Zeng, L., Dhalluin, C., Ashton, R., & Zhou, M.-M.
Affiliations
New York University (US)
Corresponding author
Zhou, Ming-Ming
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2001-02
Volume
7
Issue
2
Pages
387-399
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/s1097-2765(01)00186-1
OpenAlex
W2111222398
Cited by
119
References
52
Citations by year
2025: 5 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 5
FWCI
3.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca080938-05)
  • National Cancer Institute (CA 80938)
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 › Protein Structure and Dynamics
Keywords
MKP-3, MAPK phosphatase, ERK2, dual-specificity phosphatase, phosphatase activation, conformational change, substrate specificity, solution structure, mitogenic signaling
MeSH terms
Amino Acid Sequence, Binding Sites, Enzyme Activation, Humans, Models, Biological, Models, Molecular, Molecular Sequence Data, Protein Binding, Recombinant Fusion Proteins, Blotting, Western, Mutagenesis, Sequence Alignment, Protein Tyrosine Phosphatases, Protein Structure, Secondary, Protein Structure, Tertiary, Nuclear Magnetic Resonance, Biomolecular, Mitogen-Activated Protein Kinase 1, Catalytic Domain, Dual Specificity Phosphatase 6, Static Electricity

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