Cited by 321Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingProtein Structure and Dynamics

Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2

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Barford, David, Neel, Benjamin G·1998·Structure

Abstract

The crystal structure of the protein tyrosine phosphatase SHP-2 reveals the mechanism of auto-inhibition of phosphatase activity by its SH2 domains. Phosphotyrosine peptide stimulation of the phosphatase activity, resulting from peptide binding to the N-terminal SH2 domain, is linked to conformational changes within the protein, including an unprecedented allosteric transition of the N-terminal SH2 domain.

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Registry

Crossref · 10.1016/s0969-2126(98)00027-6

Cites

33 of 33 references verified0 citation errors · 0 not checkable

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  • SHP2 contains two SH2 domains (N-SH2 and C-SH2) at N-terminal, a catalytic PTP domain, and two phosphorylable tyrosine residues (Tyr542 and Tyr580) at C-terminal.

    “Structurally, SHP2 contains two SH2 domains (N-SH2 and C-SH2) at the N-terminal, a catalytic PTP domain, and two phosphorylable tyrosine residues (Tyr542 and Tyr580) at the C-terminal.”

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Authors
Barford, D., & Neel, B. G.
Affiliations
  • University of Oxford (GB)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
Neel, Benjamin G
Venue
Structure
Publisher
Elsevier BV
Published
1998-03
Volume
6
Issue
3
Pages
249-254
ISSN
0969-2126 (ISSN-L)
OpenAlex
W2093762625
Cited by
321
References
33
Citations by year
2026: 12 · 2025: 14 · 2024: 14 · 2023: 22 · 2022: 11 · 2021: 12 · 2020: 30 · 2019: 10 · 2018: 13 · 2017: 11 · 2016: 9 · 2015: 9 · 2014: 6 · 2013: 16 · 2012: 7
FWCI
0.65
Type
journal article
Language
en
Open access
Locations
  • Structure (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 › Protein Structure and Dynamics
Keywords
SHP2, protein tyrosine phosphatase, SH2 domain, autoinhibition, allosteric transition, conformational change, crystal structure, enzyme regulation
MeSH terms
Enzyme Activation, Models, Molecular, Protein Conformation, Signal Transduction, Protein Tyrosine Phosphatases, src Homology Domains, Intracellular Signaling Peptides and Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatase, Non-Receptor Type 11, SH2 Domain-Containing Protein Tyrosine Phosphatases

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