ArticleNature communications2023
Oncogenic mutations of PIK3CA lead to increased membrane recruitment driven by reorientation of the ABD, p85 and C-terminus.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- PI3K signaling in breast cancer: therapeutic advances versus adaptive resistance.The Journal of clinical investigation · 2026Review
- Exceptional response to alpelisib in a heavily pretreated patient with metastatic breast cancer carrying a PIK3CA mutation outside SOLAR-1 eligible mutations: a case report.Acta oncologica (Stockholm, Sweden) · 2026Article
- Protein-protein interactions as therapeutic targets in breast cancer: integrated computational and experimental advances, mechanisms and clinical translation.Molecular biology reports · 2026Review
- Commentary beyond the ATP site: Cryo-EM views of allosteric PI3KActa pharmaceutica Sinica. B · 2026Article
- Molecular architecture responsible for specific inhibition of oncogenic PI3KActa pharmaceutica Sinica. B · 2026Article
- Structures of the PI3Kα/KRas complex on lipid bilayers reveal molecular mechanisms of PI3Kα activation.Molecular cell · 2026Article
- COSMIC-Linked Ras Mutations at the Interface Between H-Ras and PI3KγBiochemistry · 2026Article
- COSMIC-Linked Ras Mutations at the Interface Between H-Ras and PI3KγbioRxiv : the preprint server for biology · 2026Article
- The proximal lipid phase of PI3K signaling is confined to the plasma membrane.bioRxiv : the preprint server for biology · 2026Article
- Use of hydrogen deuterium exchange mass spectrometry in tandem with modern structural biology.The Biochemical journal · 2026Review
- LC-MS/MS-based metabolomics analysis and experimental verification reveal the mechanism of Dahuang Mudan Decoction inhibition with the proliferation of colorectal cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Predicting protein cascade expression from H&E images.PLoS computational biology · 2026Article
- A new functional assay reveals that membrane binding is critical for overactivation of the phosphoinositide 3-kinase H1047R mutant.The Journal of biological chemistry · 2026Article
- Cell-free DNA in precision medicine: overcoming biological barriers through integrated nanoparticle platforms for simultaneous diagnosis and therapy.Journal of nanobiotechnology · 2026Review
- Predicting Protein Cascade Expression from H&E Images.medRxiv : the preprint server for health sciences · 2026Article
- Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets.Communications chemistry · 2026Article
- Understanding the distinct role of PI3K(p110Frontiers in cardiovascular medicine · 2026Review
- Recurrent somatic copy number alterations in resected cerebral cavernous malformations.Human genomics · 2025Article
- Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets.bioRxiv : the preprint server for biology · 2025Article
- Analysis and Interpretation of Somatic NMD-Escaping Variants in Oncogenes and Dual-Function Genes across Adult and Pediatric Cancer Cohorts.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PIK3CA encoding the phosphoinositide 3-kinase (PI3K) p110α catalytic subunit is frequently mutated in cancer, with mutations occurring widely throughout the primary sequence. The full set of mechanisms underlying how PI3Ks are activated by all oncogenic mutations on membranes are unclear. Using a synergy of biochemical assays and hydrogen deuterium exchange mass spectrometry (HDX-MS), we reveal unique regulatory mechanisms underlying PI3K activation. Engagement of p110α on membranes leads to disengagement of the ABD of p110α from the catalytic core, and the C2 domain from the iSH2 domain of the p85 regulatory subunit. PI3K activation also requires reorientation of the p110α C-terminus, with mutations that alter the inhibited conformation of the C-terminus increasing membrane binding. Mutations at the C-terminus (M1043I/L, H1047R, G1049R, and N1068KLKR) activate p110α through distinct mechanisms, with this having important implications for mutant selective inhibitor development. This work reveals unique mechanisms underlying how PI3K is activated by oncogenic mutations, and explains how double mutants can synergistically increase PI3K activity.
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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.