ArticleNature communications2025
Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- RAS-PI3Kα signaling regulates KrasG12D-induced lymphangiogenesis in complex lymphatic anomalies.Disease models & mechanisms · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- MEN1 Deficiency Drives Lung Cancer Progression via Activation of MMP10-Mediated Angiogenesis.Cancer science · 2026Article
- Structures of the PI3Kα/KRas complex on lipid bilayers reveal molecular mechanisms of PI3Kα activation.Molecular cell · 2026Article
- Evolution of KRAS molecular glues: from allele-selective to Pan-RAS and protein-protein interaction modulators.Acta pharmacologica Sinica · 2026Review
- COSMIC-Linked Ras Mutations at the Interface Between H-Ras and PI3KγBiochemistry · 2026Article
- Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- COSMIC-Linked Ras Mutations at the Interface Between H-Ras and PI3KγbioRxiv : the preprint server for biology · 2026Article
- Revisiting RAS family GTPase signaling: effector selectivity and oncogenic bypass.The Biochemical journal · 2026Review
- RRAS and RRAS2 Mutations Are Recurrent Oncogenic Drivers in Lung Cancer and Are Sensitive to the Pan-RAS Inhibitor RMC-6236.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Aging, dauer, and stature phenotypes are conferred by structure-directed missense mutations in the endogenous AGE-1/phosphatidylinositol 3-kinase catalytic subunit.bioRxiv : the preprint server for biology · 2026Article
- Structure of SHOC2-KRAS-PP1C complex reveals RAS isoform-specific determinants and insights into targeting complex assembly by RAS inhibitors.Nature communications · 2026Article
- Vascular malformations: from genetics to therapeutics.EMBO molecular medicine · 2026Review
- KRAS Codon-Specific Mutations Differentially Toggle PI3K Pathway Signaling and Alter Sensitivity to Inavolisib (GDC-0077).Molecular cancer therapeutics · 2025Article
- NRas Nanoclusters Mediate Crosstalk Between BRAF/ERK and PI3K/AKT Signaling in Melanoma Cells.International journal of molecular sciences · 2025Article
- Structural and allosteric effects of the membrane-bound PI3Kα H1047R mutation and opportunities for drug discovery.Communications chemistry · 2025Article
- Precise regulation of RAS-Mediated PI3Kα activation: therapeutic potential of BBO-10203 in cancer treatment.Experimental hematology & oncology · 2025Article
- M-Ras distinct activation scenarios: A mechanistic outlook and targeting.Computational and structural biotechnology journal · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Mutations in RAS and PI3Kα are major drivers of human cancer. Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway. Disrupting RAS-PI3Kα interaction enhances survival in lung and skin cancer models and reduces tumor growth and angiogenesis, although the structural details of this interaction remain unclear. Here, we present structures of KRAS, RRAS2, and MRAS bound to the catalytic subunit (p110α) of PI3Kα, elucidating the interaction interfaces and local conformational changes upon complex formation. Structural and mutational analyses highlighted key residues in RAS and PI3Kα impacting binding affinity and revealed isoform-specific differences at the interaction interface in RAS and PI3K isoforms, providing a rationale for their differential affinities. Notably, in the RAS-p110α complex structures, RAS interaction with p110α is limited to the RAS-binding domain and does not involve the kinase domain. This study underscores the pivotal role of the RAS-PI3Kα interaction in PI3Kα activation and provides a blueprint for designing PI3Kα isoform-specific inhibitors to disrupt this interaction.
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