ArticleNature2013
Temporal regulation of EGF signalling networks by the scaffold protein Shc1.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 1 of them a synthesis that pooled it.
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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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
170 citing papers in PubMed, 1 synthesis or guideline pooled it, 291 citations in OpenAlex.
- Differential transcriptional effects of EGFR inhibitors.PloS one · 2014Pooled it
- Proteomic investigation of signaling dynamics: from static maps to network rewiring.Bioscience reports · 2026Review
- A ternary association of KRas, EphA2, and integrins controls PDAC cell behavior.The Journal of biological chemistry · 2026Article
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- Systematic optimization and benchmarking of synchro-PASEF for high-throughput phosphoproteome profiling.bioRxiv : the preprint server for biology · 2026Article
- HNature chemical biology · 2026Article
- A tandem recruitment site in the pseudokinase scaffold PEAK3 is subject to phosphorylation-dependent regulation and cancer-associated mutations.The Journal of biological chemistry · 2026Article
- AXL-SHC1 signaling axis mediates adaptive resistance to HER2-targeted tyrosine kinase inhibitors in HER2-aberrant lung and gastric cancers.NPJ precision oncology · 2026Article
- A Brief Progress in Methods for Deciphering Protein-Protein Interaction Networks.International journal of molecular sciences · 2026Review
- Article
- Non-canonical EGFR signaling promotes MAPK-dependent extrusion of epithelial cells.Journal of cell science · 2025Article
- SHIP2-PLK1 crosstalk promotes sensitivity to dual inhibition in esophageal squamous cell carcinoma.Molecular cancer · 2025Article
- Integrative Proteogenomics and Forward Genetics Reveal a Novel Mitotic Vulnerability in Triple-Negative Breast Cancer.Cancer discovery · 2025Article
- The Roles of SHCBP1 in Cancer Hallmarks: Molecular Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Tensins in Cancer: Integration of Their Domain Functions, Context-Dependent Regulation and Biomarker Potential.Biology · 2025Review
- Current understanding of PEAK family members in regulation of cellular signaling pathways and cancer therapy.Molecular and cellular biochemistry · 2025Review
- Peptide Family Promotes Brain Cell Rejuvenation and Improved Cognition through Peripheral Delivery.ACS omega · 2025Article
- Activation of CAMK2 by pseudokinase PEAK1 represents a targetable pathway in triple negative breast cancer.Nature communications · 2025Article
- SHCBP1 promotes cisplatin resistance of ovarian cancer through AKT/mTOR/Autophagy pathway.Apoptosis : an international journal on programmed cell death · 2025Article
- Bioeliminable Pt@BiTheranostics · 2025Article
110 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 5 countries.
Funding
Abstract
Cell-surface receptors frequently use scaffold proteins to recruit cytoplasmic targets, but the rationale for this is uncertain. Activated receptor tyrosine kinases, for example, engage scaffolds such as Shc1 that contain phosphotyrosine (pTyr)-binding (PTB) domains. Using quantitative mass spectrometry, here we show that mammalian Shc1 responds to epidermal growth factor (EGF) stimulation through multiple waves of distinct phosphorylation events and protein interactions. After stimulation, Shc1 rapidly binds a group of proteins that activate pro-mitogenic or survival pathways dependent on recruitment of the Grb2 adaptor to Shc1 pTyr sites. Akt-mediated feedback phosphorylation of Shc1 Ser 29 then recruits the Ptpn12 tyrosine phosphatase. This is followed by a sub-network of proteins involved in cytoskeletal reorganization, trafficking and signal termination that binds Shc1 with delayed kinetics, largely through the SgK269 pseudokinase/adaptor protein. Ptpn12 acts as a switch to convert Shc1 from pTyr/Grb2-based signalling to SgK269-mediated pathways that regulate cell invasion and morphogenesis. The Shc1 scaffold therefore directs the temporal flow of signalling information after EGF stimulation.
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What OpenQuestion holds
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.