ArticleScientific reports2020
An allosteric interaction controls the activation mechanism of SHP2 tyrosine phosphatase.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- SHP2 as a pivotal modulator of the tumor microenvironment in gastrointestinal cancers: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- Cancer-Causing Mutations Alter the Interplay Between Loop Dynamics and Catalysis in the Protein Tyrosine Phosphatases SHP-1 and SHP-2.bioRxiv : the preprint server for biology · 2026Article
- Phosphatase SHP2 pathogenic mutations enhance activity by altering conformational sampling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Phosphatase SHP2 pathogenic mutations enhance activity by altering conformational sampling.bioRxiv : the preprint server for biology · 2025Article
- Orchestrating function: Concerted dynamics, allostery, and catalysis in protein tyrosine phosphatases.Current opinion in structural biology · 2025Review
- Prodrug Strategy for PROTACs: High Efficiency and Low Toxicity.ACS omega · 2025Review
- Deciphering the structural and dynamic effects of SHP2-E76 mutations: mechanistic insights into oncogenic activation.BMC chemistry · 2025Article
- Phosphopeptide binding to the N-SH2 domain of tyrosine phosphatase SHP2 correlates with the unzipping of its central β-sheet.Computational and structural biotechnology journal · 2024Article
- The pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2.Cellular and molecular life sciences : CMLS · 2024Article
- The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2.Research square · 2024Article
- Folding and Binding Kinetics of the Tandem of SH2 Domains from SHP2.International journal of molecular sciences · 2024Article
- Targeting SHP2 Cryptic Allosteric Sites for Effective Cancer Therapy.International journal of molecular sciences · 2024Article
- The pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.bioRxiv : the preprint server for biology · 2024Article
- Single Ion Pair Is Essential for Stabilizing SHP2's Open Conformation.Biochemistry · 2024Article
- Atomistic ensemble of active SHP2 phosphatase.Communications biology · 2023Article
- SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.Cellular and molecular life sciences : CMLS · 2023Article
- Experiment-guided molecular simulations define a heterogeneous structural ensemble for theChemical science · 2023Article
- How a single mutation alters the protein structure: a simulation investigation on protein tyrosine phosphatase SHP2.RSC advances · 2023Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
SHP2 is a protein tyrosine phosphatase (PTP) involved in multiple signaling pathways. Mutations of SHP2 can result in Noonan syndrome or pediatric malignancies. Inhibition of wild-type SHP2 represents a novel strategy against several cancers. SHP2 is activated by binding of a phosphopeptide to the N-SH2 domain of SHP2, thereby favoring dissociation of the N-SH2 domain and exposing the active site on the PTP domain. The conformational transitions controlling ligand affinity and PTP dissociation remain poorly understood. Using molecular simulations, we revealed an allosteric interaction restraining the N-SH2 domain into a SHP2-activating and a stabilizing state. Only ligands selecting for the activating N-SH2 conformation, depending on ligand sequence and binding mode, are effective activators. We validate the model of SHP2 activation by rationalizing modified basal activity and responsiveness to ligand stimulation of several N-SH2 variants. This study provides mechanistic insight into SHP2 activation and may open routes for SHP2 regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.