ArticleeLife2023
High-throughput profiling of sequence recognition by tyrosine kinases and SH2 domains using bacterial peptide display.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 24 citations in OpenAlex.
- Substrate-Derived Peptides for Selective Covalent Inhibition of Protein Tyrosine Kinases.ACS chemical biology · 2026Article
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- Synthetic Substrate Discovery for Hck Kinase via Phage Display.Biochemistry · 2026Article
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Context-dependent peptide recognition shapes tyrosine kinase substrate specificity beyond consensus motifs.bioRxiv : the preprint server for biology · 2026Article
- Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.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
- Molecular determinants of differential substrate selection between the Src family kinases Lck and Src.Frontiers in immunology · 2026Article
- Profiling tyrosine kinase substrate recognition using bacterial peptide display and deep sequencing.bioRxiv : the preprint server for biology · 2025Article
- Accurate affinity models for SH2 domains from peptide binding assays and free-energy regression.Protein science : a publication of the Protein Society · 2025Article
- Synthetic signaling platform uncovers and rewires cellular responses to PD-1 perturbation.bioRxiv : the preprint server for biology · 2025Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Development of a Peptide Inhibitor Targeting the C-SH2 Domain of the SHP2 Phosphatase.Chembiochem : a European journal of chemical biology · 2025Article
- R2HaPpY: Rapid-robust phosphotyrosine peptide enrichment using HaloTag-Src SH2 pY superbinder.bioRxiv : the preprint server for biology · 2025Article
- Reaching New Heights in Genetic Code Manipulation with High Throughput Screening.Chemical reviews · 2024Review
- A quantitative intracellular peptide binding assay reveals recognition determinants and context dependence of short linear motifs.bioRxiv : the preprint server for biology · 2024Article
- The fitness cost of spurious phosphorylation.The EMBO journal · 2024Article
- The prospect of substrate-based kinase inhibitors to improve target selectivity and overcome drug resistance.Chemical science · 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
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tyrosine kinases and SH2 (phosphotyrosine recognition) domains have binding specificities that depend on the amino acid sequence surrounding the target (phospho)tyrosine residue. Although the preferred recognition motifs of many kinases and SH2 domains are known, we lack a quantitative description of sequence specificity that could guide predictions about signaling pathways or be used to design sequences for biomedical applications. Here, we present a platform that combines genetically encoded peptide libraries and deep sequencing to profile sequence recognition by tyrosine kinases and SH2 domains. We screened several tyrosine kinases against a million-peptide random library and used the resulting profiles to design high-activity sequences. We also screened several kinases against a library containing thousands of human proteome-derived peptides and their naturally-occurring variants. These screens recapitulated independently measured phosphorylation rates and revealed hundreds of phosphosite-proximal mutations that impact phosphosite recognition by tyrosine kinases. We extended this platform to the analysis of SH2 domains and showed that screens could predict relative binding affinities. Finally, we expanded our method to assess the impact of non-canonical and post-translationally modified amino acids on sequence recognition. This specificity profiling platform will shed new light on phosphotyrosine signaling and could readily be adapted to other protein modification/recognition domains.
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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.