Cited by 140Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingMelanoma and MAPK Pathways

Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3

Liu, Sijiu, Sun, Jin-Peng, Zhou, Bo, Zhang, Zhong-Yin·2006·Proceedings of the National Academy of Sciences

Abstract

Mitogen-activated protein (MAP) kinases are central components of signal transduction pathways for cell proliferation, stress responses, and differentiation. Signaling efficiency and specificity are modulated in large part by docking interactions between individual MAP kinase and the kinase interaction motif (KIM), (R/K) 2–3 -X 1–6 -Φ A -X-Φ B , in its cognate kinases, phosphatases, scaffolding proteins, and substrates. We have determined the crystal structure of extracellular signal-regulated protein kinase 2 bound to the KIM peptide from MAP kinase phosphatase 3, an extracellular signal-regulated protein kinase 2-specific phosphatase. The structure reveals that the KIM docking site, situated in a noncatalytic region opposite of the kinase catalytic pocket, is comprised of a highly acidic patch and a hydrophobic groove, which engage the basic and Φ A -X-Φ B residues, respectively, in the KIM sequence. The specific docking interactions observed in the structure consolidate all known biochemical data. In addition, structural comparison indicates that the KIM docking site is conserved in all MAP kinases. The results establish a structural model for understanding how MAP kinases interact with their regulators and substrates and provide new insights into how MAP kinase docking specificity can be achieved.

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Crossref · 10.1073/pnas.0510506103

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Authors
Liu, S., Sun, J.-P., Zhou, B., & Zhang, Z.-Y.
Affiliations
Indiana University School of Medicine (US)
Venue
Proceedings of the National Academy of Sciences
Published
2006-04-04
Volume
103
Issue
14
Pages
5326-5331
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2030976054
Cited by
140
References
36
Citations by year
2026: 7 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 11 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 8 · 2015: 5 · 2014: 3 · 2013: 11 · 2012: 14
FWCI
4.22
Type
journal article
Language
en
Open access
closed
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA-69202, R01CA069202)
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, MAPK signaling, crystal structure, acidic patch, hydrophobic groove, protein-protein interaction
MeSH terms
Amino Acid Sequence, Binding Sites, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Tyrosine Phosphatases, Sequence Homology, Amino Acid, Mitogen-Activated Protein Kinase 1, Amino Acid Motifs, Dual Specificity Phosphatase 6

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