ArticleCancer research2016
An Atlas of the Human Kinome Reveals the Mutational Landscape Underlying Dysregulated Phosphorylation Cascades in Cancer.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Combinatorial Targeting of Avapritinib-Driven MAP Kinase Activation in High-Grade Glioma.Research square · 2026Article
- A reversible SRC-relayed COX2 inflammatory program drives resistance to BRAF and EGFR inhibition in BRAFNature cancer · 2023Article
- Response and resistance to BRAFFrontiers in oncology · 2022Review
- MAPPINGS, a tool for network analysis of large phospho-signalling datasets: application to host erythrocyte response toCurrent research in microbial sciences · 2022Article
- A protein interaction landscape of breast cancer.Science (New York, N.Y.) · 2021Article
- Copy number aberrations drive kinase rewiring, leading to genetic vulnerabilities in cancer.Cell reports · 2021Article
- Pathogenic missense protein variants affect different functional pathways and proteomic features than healthy population variants.PLoS biology · 2021Article
- Kinomic profile in patient-derived glioma cells during hypoxia reveals c-MET-PI3K dependency for adaptation.Theranostics · 2021Article
- A census of pathway maps in cancer systems biology.Nature reviews. Cancer · 2020Review
- Using phosphoproteomics data to understand cellular signaling: a comprehensive guide to bioinformatics resources.Clinical proteomics · 2020Review
- A STAT3-based gene signature stratifies glioma patients for targeted therapy.Nature communications · 2019Article
- Mapping phospho-catalytic dependencies of therapy-resistant tumours reveals actionable vulnerabilities.Nature cell biology · 2019Article
- Platination of cysteine by an epidermal growth factor receptor kinase-targeted hybrid agent.Chemical communications (Cambridge, England) · 2018Article
- Computational Structural Biology ofFrontiers in oncology · 2018Review
- Analysis of somatic mutations across the kinome reveals loss-of-function mutations in multiple cancer types.Scientific reports · 2017Article
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Authors and funding
10 authors.
Funding
Abstract
Kinase inhibitors are used widely to treat various cancers, but adaptive reprogramming of kinase cascades and activation of feedback loop mechanisms often contribute to therapeutic resistance. Determining comprehensive, accurate maps of kinase circuits may therefore help elucidate mechanisms of response and resistance to kinase inhibitor therapies. In this study, we identified and validated phosphorylatable target sites across human cell and tissue types to generate PhosphoAtlas, a map of 1,733 functionally interconnected proteins comprising the human phospho-reactome. A systematic curation approach was used to distill protein phosphorylation data cross-referenced from 38 public resources. We demonstrated how a catalog of 2,617 stringently verified heptameric peptide regions at the catalytic interface of kinases and substrates could expose mutations that recurrently perturb specific phospho-hubs. In silico mapping of 2,896 nonsynonymous tumor variants identified from thousands of tumor tissues also revealed that normal and aberrant catalytic interactions co-occur frequently, showing how tumors systematically hijack, as well as spare, particular subnetworks. Overall, our work provides an important new resource for interrogating the human tumor kinome to strategically identify therapeutically actionable kinase networks that drive tumorigenesis. Cancer Res; 76(7); 1733-45. ©2016 AACR.
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