Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2
Open accessAbstract
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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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.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [269]
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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
- bronze
- doi.org
- Licence
- 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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