Cited by 63Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingMelanoma and MAPK Pathways

Mitogen-activated Protein Kinase (MAPK) Phosphatase 3-mediated Cross-talk between MAPKs ERK2 and p38α

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Zhang, Yuan-Yuan, Wu, Jia-Wei, Wang, Zhi-Xin·2011·Journal of Biological Chemistry

Abstract

MAPK phosphatase 3 (MKP3) is highly specific for ERK1/2 inactivation via dephosphorylation of both phosphotyrosine and phosphothreonine critical for enzymatic activation. Here, we show that MKP3 is able to effectively dephosphorylate the phosphotyrosine, but not phosphothreonine, in the activation loop of p38α in vitro and in intact cells. The catalytic constant of the MKP3 reaction for p38α is comparable with that for ERK2. Remarkably, MKP3, ERK2, and phosphorylated p38α can form a stable ternary complex in solution, and the phosphatase activity of MKP3 toward p38α substrate is allosterically regulated by ERK2-MKP3 interaction. This suggests that MKP3 not only controls the activities of ERK2 and p38α but also mediates cross-talk between these two MAPK pathways. The crystal structure of bisphosphorylated p38α has been determined at 2.1 Å resolution. Comparisons between the phosphorylated MAPK structures reveal the molecular basis of MKP3 substrate specificity.

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Crossref · 10.1074/jbc.m110.203786

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  • Despite their high sequence similarity, HePTP, STEP, and PTPSL regulate/deactivate p38 with different efficiencies.

    “Despite their high sequence similarity, it has been shown that these three phosphatases regulate/deactivate p38 with different efficiencies.76”

    From Molecular basis of MAP kinase regulation (2013) · cites this paper as [76]

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Authors
Zhang, Y.-Y., Wu, J.-W., & Wang, Z.-X.
Affiliations
Chinese Academy of Sciences (CN)
Corresponding author
Wang, Zhi-Xin
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2011-05
Volume
286
Issue
18
Pages
16150-16162
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1965902294
Cited by
63
References
50
Citations by year
2026: 7 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 10 · 2013: 6 · 2012: 7
FWCI
3.24
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • 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
MKP-3, ERK2, p38α, dephosphorylation, substrate specificity, allosteric regulation, ternary complex, phosphotyrosine, phosphothreonine
MeSH terms
Animals, Humans, Phosphorylation, Substrate Specificity, Protein Structure, Tertiary, Crystallography, X-Ray, Mitogen-Activated Protein Kinase 1, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Mice, Dual Specificity Phosphatase 6, HEK293 Cells

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