ArticleNature structural & molecular biology2015
EGF-receptor specificity for phosphotyrosine-primed substrates provides signal integration with Src.
Article in Nature structural & molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Androgen rapidly activates phosphorylation signaling pathways in Sertoli cells.Experimental and therapeutic medicine · 2026Article
- Construction and validation of an EGFR-related risk signature identifiedTranslational cancer research · 2025Article
- Structural Identification of Major Molecular Determinants for Phosphotyrosine Recognition in Tyrosine Kinases Reveals Tumour Promoting and Suppressive Functions.bioRxiv : the preprint server for biology · 2025Article
- Article
- A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition.NPJ precision oncology · 2024Article
- MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling.Molecular cancer therapeutics · 2024Article
- Article
- Dual data and motif clustering improves the modeling and interpretation of phosphoproteomic data.Cell reports methods · 2022Article
- Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution.Nature communications · 2021Article
- The intracellular domains of the EphB6 and EphA10 receptor tyrosine pseudokinases function as dynamic signalling hubs.The Biochemical journal · 2021Article
- ExploringMicrobial cell (Graz, Austria) · 2021Review
- MERTK Inhibition: Potential as a Treatment Strategy in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Role of EGF Receptor Regulatory Networks in the Host Response to Viral Infections.Frontiers in cellular and infection microbiology · 2021Review
- 1‑Palmitoyl‑2‑linoleoyl‑3‑acetyl‑rac‑glycerol ameliorates EGF‑induced MMP‑9 expression by promoting receptor desensitization in MDA‑MB‑231 cells.Oncology reports · 2020Article
- Substrate binding to Src: A new perspective on tyrosine kinase substrate recognition from NMR and molecular dynamics.Protein science : a publication of the Protein Society · 2020Article
- Structure-based inhibitory peptide design targeting peptide-substrate binding site in EGFR tyrosine kinase.PloS one · 2019Article
- Substrate priming enhances phosphorylation by the budding yeast kinases Kin1 and Kin2.The Journal of biological chemistry · 2018Article
- Overcoming EGFRNature communications · 2018Article
- The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine kinases.Critical reviews in biochemistry and molecular biology · 2018Review
- Deep mutational analysis reveals functional trade-offs in the sequences of EGFR autophosphorylation sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
Aberrant activation of the EGF receptor (EGFR) contributes to many human cancers by activating the Ras-MAPK pathway and other pathways. EGFR signaling is augmented by Src-family kinases, but the mechanism is poorly understood. Here, we show that human EGFR preferentially phosphorylates peptide substrates that are primed by a prior phosphorylation. Using peptides based on the sequence of the adaptor protein Shc1, we show that Src mediates the priming phosphorylation, thus promoting subsequent phosphorylation by EGFR. Importantly, the doubly phosphorylated Shc1 peptide binds more tightly than singly phosphorylated peptide to the Ras activator Grb2; this binding is a key step in activating the Ras-MAPK pathway. Finally, a crystal structure of EGFR in complex with a primed Shc1 peptide reveals the structural basis for EGFR substrate specificity. These results provide a molecular explanation for the integration of Src and EGFR signaling with downstream effectors such as Ras.
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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.