ArticleeLife2018
Fine-tuning of substrate preferences of the Src-family kinase Lck revealed through a high-throughput specificity screen.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- Molecular determinants of differential substrate selection between the Src family kinases Lck and Src.Frontiers in immunology · 2026Article
- Bacterial EPIYA/EPIYA-like effector motifs and host regulatory pY-SH2 logic: a sequence-informed three-layer convergence model.Frontiers in cellular and infection microbiology · 2026Article
- Profiling tyrosine kinase substrate recognition using bacterial peptide display and deep sequencing.bioRxiv : the preprint server for biology · 2025Article
- Low Levels of Mouse γδ T Cell Development Persist in the Presence of Null Mutants of the LAT Adaptor.International journal of molecular sciences · 2025Article
- Uncovering the molecular basis of kinase activity and substrate recognition with phospho-PCA.bioRxiv : the preprint server for biology · 2025Article
- An engineered viral protein activates STAT5 to prevent T cell suppression.Science immunology · 2025Article
- The fitness cost of spurious phosphorylation.The EMBO journal · 2024Article
- The quantum model of T-cell activation: Revisiting immune response theories.Scandinavian journal of immunology · 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 pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.bioRxiv : the preprint server for biology · 2024Article
- Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail.Nature communications · 2024Article
- Recent advances on CAR-T signaling pave the way for prolonged persistence and new modalities in clinic.Frontiers in immunology · 2024Review
- Article
- Dissecting signaling regulators driving AXL-mediated bypass resistance and associated phenotypes by phosphosite perturbations.bioRxiv : the preprint server for biology · 2023Article
- The fitness cost of spurious phosphorylation.bioRxiv : the preprint server for biology · 2023Article
- Control of atypical PKCι membrane dissociation by tyrosine phosphorylation within a PB1-C1 interdomain interface.The Journal of biological chemistry · 2023Article
- Regulation of PD-L1 Expression by Nuclear Receptors.International journal of molecular sciences · 2023Review
- Marginal specificity in protein interactions constrains evolution of a paralogous family.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
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Authors and funding
4 authors.
Funding
Abstract
The specificity of tyrosine kinases is attributed predominantly to localization effects dictated by non-catalytic domains. We developed a method to profile the specificities of tyrosine kinases by combining bacterial surface-display of peptide libraries with next-generation sequencing. Using this, we showed that the tyrosine kinase ZAP-70, which is critical for T cell signaling, discriminates substrates through an electrostatic selection mechanism encoded within its catalytic domain (Shah et al., 2016). Here, we expand this high-throughput platform to analyze the intrinsic specificity of any tyrosine kinase domain against thousands of peptides derived from human tyrosine phosphorylation sites. Using this approach, we find a difference in the electrostatic recognition of substrates between the closely related Src-family kinases Lck and c-Src. This divergence likely reflects the specialization of Lck to act in concert with ZAP-70 in T cell signaling. These results point to the importance of direct recognition at the kinase active site in fine-tuning specificity.
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