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Cited by 33Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingMelanoma and MAPK Pathways

Two Clusters of Residues at the Docking Groove of Mitogen-activated Protein Kinases Differentially Mediate Their Functional Interaction with the Tyrosine Phosphatases PTP-SL and STEP

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Tárrega, Céline, Blanco-Aparicio, Carmen, Muñoz, Juan José, Pulido, Rafael·2002·Journal of Biological Chemistry
DOI 10.1074/jbc.m108874200
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Abstract

Regulated function of mitogen-activated protein (MAP) kinases involves their selective association through docking sites with both activating MAP kinase kinases and inactivating phosphatases, including dual specificity and protein-tyrosine phosphatases (PTP). Site-directed mutagenesis on the mammalian MAP kinases ERK2 and p38alpha identified within their C-terminal docking grooves two clusters of residues important for association with their regulatory PTPs, PTP-SL and STEP. ERK2 and p38alpha mutations that resembled the sevenmaker gain-of-function mutation in the Rolled D. melanogaster ERK2 homologue failed to associate with PTP-SL, were not retained in the cytosol, and were poorly inactivated by this PTP. Additional ERK2 mutations at the docking groove showed deficient association and dephosphorylation by PTP-SL, although their cytosolic retention was unaffected. Other ERK2 mutations, resembling gain-of-function mutations in the FUS3 yeast ERK2 homologue, associated to PTP-SL and were inactivated normally by this PTP. Our results demonstrate that mutations at distinct regions of the docking groove of ERK2 and p38alpha differentially affect their association and regulation by the PTP-SL and STEP PTPs.

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  • While the KIM is required for binding, residues outside the KIM contribute to both binding and specificity.

    “While the KIM is required for binding, 38,39 multiple reports have shown that residues outside the KIM contribute to both binding and specificity.40,41”

    From Molecular basis of MAP kinase regulation (2013) · cites this paper as [41]

  • KIM sequences that contain conserved basic and hydrophobic residues, and are part of the well-folded MKBD of typical DUSPs, engage the common complementary KIM-binding groove in MAPKs.

    “It was hypothesized that the KIM sequences that contain conserved basic and hydrophobic residues, and are part of the well-folded MKBD of the typical DUSPs, engage the common complementary KIM-binding groove in MAPKs.41,44 This was only recently confirmed”

    From Molecular basis of MAP kinase regulation (2013) · cites this paper as [41]

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Authors
Tárrega, C., Blanco-Aparicio, C., Muñoz, J. J., & Pulido, R.
Corresponding author
Pulido, Rafael
ORCID
Pulido, Rafael
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-01
Volume
277
Issue
4
Pages
2629-2636
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m108874200
OpenAlex
W2001959826
Cited by
33
References
71
Citations by year
2025: 1 · 2023: 2 · 2021: 1 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 4
FWCI
1.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • 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
mitogen-activated protein kinase, STEP, protein tyrosine phosphatase, ERK2, p38α, protein-protein interaction, dephosphorylation, FUS3, MAP kinase kinase
MeSH terms
Amino Acid Sequence, Animals, Binding Sites, Cell Line, Cells, Cultured, Cytosol, Dose-Response Relationship, Drug, Drosophila, Electrophoresis, Polyacrylamide Gel, Epidermal Growth Factor, Glutathione Transferase, Humans, Microscopy, Fluorescence, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Phosphorylation, Precipitin Tests, Protein Binding, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Time Factors, Transfection, Immunoblotting, Signal Transduction, Mutagenesis, Site-Directed, Protein Tyrosine Phosphatases, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Mice, Protein Tyrosine Phosphatases, Non-Receptor, Receptor-Like Protein Tyrosine Phosphatases, Class 7

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