ArticleNature structural & molecular biology2016
Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking.
Article in Nature structural & molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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
61 citing papers in PubMed, 113 citations in OpenAlex.
- InstaNovo-P: a de novo peptide sequencing model for phosphoproteomics.Nature communications · 2026Article
- Multiomics analysis reveals dermokine as a regulator of keratinocyte differentiation and adhesion.JCI insight · 2026Article
- R2HaPpY: Rapid-robust phosphotyrosine peptide enrichment using HaloTag-Src SH2 pY superbinder.bioRxiv : the preprint server for biology · 2025Article
- Phosphorylation on serine 72 modulates Rab7A palmitoylation and retromer recruitment.Journal of cell science · 2025Article
- Multi-layered proteomics identifies insulin-induced upregulation of the EphA2 receptor via the ERK pathway which is dependent on low IGF1R level.Scientific reports · 2024Article
- DeKinomics pulse-chases kinase functions in living cells.Nature chemical biology · 2024Article
- EMP3 sustains oncogenic EGFR/CDK2 signaling by restricting receptor degradation in glioblastoma.Acta neuropathologica communications · 2023Article
- Budding uninhibited by benzimidazoles-1 (BUB1) regulates EGFR signaling by reducing EGFR internalization.Aging · 2023Article
- Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway.Frontiers in immunology · 2023Article
- Functional selectivity of Receptor Tyrosine Kinases regulates distinct cellular outputs.Frontiers in cell and developmental biology · 2023Review
- Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival.Nature communications · 2022Article
- The emerging role of mass spectrometry-based proteomics in drug discovery.Nature reviews. Drug discovery · 2022Review
- Article
- Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached.Cell reports · 2022Article
- Time-resolved proximity labeling of protein networks associated with ligand-activated EGFR.Cell reports · 2022Article
- Major histocompatibility complex class I molecule expression by pancreatic cancer cells is regulated by activation and inhibition of the epidermal growth factor receptor.Immunologic research · 2022Article
- EPHA2 mediates PDGFA activity and functions together with PDGFRA as prognostic marker and therapeutic target in glioblastoma.Signal transduction and targeted therapy · 2022Article
- PhosPiR: an automated phosphoproteomic pipeline in R.Briefings in bioinformatics · 2022Article
- Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution.Nature communications · 2021Article
- D-Propranolol Impairs EGFR Trafficking and Destabilizes Mutant p53 Counteracting AKT Signaling and Tumor Malignancy.Cancers · 2021Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A fascinating conundrum in cell signaling is how stimulation of the same receptor tyrosine kinase with distinct ligands generates specific outcomes. To decipher the functional selectivity of EGF and TGF-α, which induce epidermal growth factor receptor (EGFR) degradation and recycling, respectively, we devised an integrated multilayered proteomics approach (IMPA). We analyzed dynamic changes in the receptor interactome, ubiquitinome, phosphoproteome, and late proteome in response to both ligands in human cells by quantitative MS and identified 67 proteins regulated at multiple levels. We identified RAB7 phosphorylation and RCP recruitment to EGFR as switches for EGF and TGF-α outputs, controlling receptor trafficking, signaling duration, proliferation, and migration. By manipulating RCP levels or phosphorylation of RAB7 in EGFR-positive cancer cells, we were able to switch a TGF-α-mediated response to an EGF-like response or vice versa as EGFR trafficking was rerouted. We propose IMPA as an approach to uncover fine-tuned regulatory mechanisms in cell signaling.
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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.