ArticleeLife2021
Time-resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of SHP2-dependent signaling.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Proteomic investigation of signaling dynamics: from static maps to network rewiring.Bioscience reports · 2026Review
- High-throughput biochemical phenotyping of SHP2 variants reveals the molecular basis of diseases and allosteric drug inhibition.bioRxiv : the preprint server for biology · 2026Article
- Decoding C‑SH2 Domain/Peptide Interactions in SH2 Domain-Containing Tyrosine Phosphatase 2: A Molecular Framework for Rational Inhibitor Design.ACS omega · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- Regulation and activity of the phosphatase SHP2: SH2 domains, dephosphorylation activity, and beyond.Biochemical Society transactions · 2026Review
- Mapping of PTP1B, TCPTP, SHP2, and Putative Substrates Reveals Novel Networks in Glomerular Podocytes.Journal of cellular physiology · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Article
- The C-type lectin receptor Dcir (Frontiers in immunology · 2025Article
- Age-related retinal degeneration resulting from the deletion of Shp2 tyrosine phosphatase in photoreceptor neurons.Cell death & disease · 2024Article
- Enzyme Is the Name-Adapter Is the Game.Cells · 2024Review
- 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
- Complex Roles ofAnnual review of cancer biology · 2024Article
- SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.bioRxiv : the preprint server for biology · 2024Article
- Phosphoproteomic investigation of targets of protein phosphatases in EGFR signaling.Scientific reports · 2024Article
- SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.Cancer discovery · 2023Review
- Phosphoproteomic Approaches for Identifying Phosphatase and Kinase Substrates.Molecules (Basel, Switzerland) · 2023Review
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- Phosphoproteomics data-driven signalling network inference: Does it work?Computational and structural biotechnology journal · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
SHP2 is a protein tyrosine phosphatase that normally potentiates intracellular signaling by growth factors, antigen receptors, and some cytokines, yet is frequently mutated in human cancer. Here, we examine the role of SHP2 in the responses of breast cancer cells to EGF by monitoring phosphoproteome dynamics when SHP2 is allosterically inhibited by SHP099. The dynamics of phosphotyrosine abundance at more than 400 tyrosine residues reveal six distinct response signatures following SHP099 treatment and washout. Remarkably, in addition to newly identified substrate sites on proteins such as occludin, ARHGAP35, and PLCγ2, another class of sites shows reduced phosphotyrosine abundance upon SHP2 inhibition. Sites of decreased phospho-abundance are enriched on proteins with two nearby phosphotyrosine residues, which can be directly protected from dephosphorylation by the paired SH2 domains of SHP2 itself. These findings highlight the distinct roles of the scaffolding and catalytic activities of SHP2 in effecting a transmembrane signaling response.
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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 Socratic graph.