ReviewFrontiers in oncology2019
Does Ras Activate Raf and PI3K Allosterically?
Review in Frontiers in oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 53 citations in OpenAlex.
- 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
- Phosphoregulation of the novel hemi-arrestin MAPK scaffold Sms1 prevents untimely mating.Nature communications · 2026Article
- Recent breakthroughs in understanding the allosteric features of Ras GTPases and their effector and regulatory protein interactions, enabling drug design.Current opinion in structural biology · 2026Review
- Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge.Journal of molecular biology · 2025Review
- Kinase signaling cascades: an updated mechanistic landscape.Chemical science · 2025Review
- Erk1Oncogene · 2025Article
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Protein conformational ensembles in function: roles and mechanisms.RSC chemical biology · 2023Review
- Binding of active Ras and its mutants to the Ras binding domain of PI-3-kinase: A quantitative approach to KAnalytical biochemistry · 2023Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- Computer-Aided Drug Design Boosts RAS Inhibitor Discovery.Molecules (Basel, Switzerland) · 2022Review
- AlphaFold, Artificial Intelligence (AI), and Allostery.The journal of physical chemistry. B · 2022Review
- Recognition of BRAF by CDC37 and Re-Evaluation of the Activation Mechanism for the Class 2 BRAF-L597R Mutant.Biomolecules · 2022Article
- The mechanism of activation of MEK1 by B-Raf and KSR1.Cellular and molecular life sciences : CMLS · 2022Article
- Mechanism of activation and the rewired network: New drug design concepts.Medicinal research reviews · 2022Review
- Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma.Biophysics reviews · 2022Review
- Integrated genotype-phenotype analysis of long-term epilepsy-associated ganglioglioma.Brain pathology (Zurich, Switzerland) · 2022Article
- The mechanism of Raf activation through dimerization.Chemical science · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism through which oncogenic Ras activates its effectors is vastly important to resolve. If allostery is at play, then targeting allosteric pathways could help in quelling activation of MAPK (Raf/MEK/ERK) and PI3K (PI3K/Akt/mTOR) cell proliferation pathways. On the face of it, allosteric activation is reasonable: Ras binding perturbs the conformational ensembles of its effectors. Here, however, we suggest that at least for Raf, PI3K, and NORE1A (RASSF5), that is unlikely. Raf's long disordered linker dampens effective allosteric activation. Instead, we suggest that the high-affinity Ras-Raf binding relieves Raf's autoinhibition, shifting Raf's ensemble from the inactive to the nanocluster-mediated dimerized active state, as Ras also does for NORE1A. PI3K is recruited and allosterically activated by RTK (e.g., EGFR) at the membrane. Ras restrains PI3K's distribution and active site orientation. It stabilizes and facilitates PIP
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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.