ArticleThe Journal of biological chemistry2011
Allosteric modulation of Ras-GTP is linked to signal transduction through RAF kinase.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 91 citations in OpenAlex.
- Selenium Nanoparticles Selectively Target KRAS G13D to Inhibit Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Computational insights on the molecular interplay between KRas (G12D mutation) and SOS1 modulated by the inhibitor BI-3406.PLoS computational biology · 2026Article
- Elucidating Ras protein as a dual therapeutic target for inflammation and cancer: a review.Discover oncology · 2025Review
- Aquaporin 9 downregulation in KRASScientific reports · 2025Article
- Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025Review
- Distinct association of HRAS and KRAS with MnMagnetic resonance letters · 2025Article
- KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways.Cells · 2024Review
- Molecular Mechanism of Phosphorylation-Mediated Impacts on the Conformation Dynamics of GTP-Bound KRAS Probed by GaMD Trajectory-Based Deep Learning.Molecules (Basel, Switzerland) · 2024Article
- Probing mutation-induced conformational transformation of the GTP/M-RAS complex through Gaussian accelerated molecular dynamics simulations.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Robust Strategy for Hit-to-Lead Discovery: NMR for SAR.Journal of medicinal chemistry · 2023Article
- Kinetic and thermodynamic allostery in the Ras protein family.Biophysical journal · 2023Article
- Allosteric site variants affect GTP hydrolysis on Ras.Protein science : a publication of the Protein Society · 2023Article
- Review
- Path Sampling Simulations Reveal How the Q61L Mutation Alters the Dynamics of KRas.The journal of physical chemistry. B · 2022Article
- Delineating the RAS Conformational Landscape.Cancer research · 2022Article
- Identification of functional substates of KRas during GTP hydrolysis with enhanced sampling simulations.Physical chemistry chemical physics : PCCP · 2022Article
- Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma.Biophysics reviews · 2022Review
- Equilibria between conformational states of the Ras oncogene protein revealed by high pressure crystallography.Chemical science · 2022Article
- KRAS G12C Mutations in NSCLC: From Target to Resistance.Cancers · 2021Review
- Engineering subtilisin proteases that specifically degrade active RAS.Communications biology · 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Ras is a key signal transduction protein in the cell. Mutants of Gly(12) and Gln(61) impair GTPase activity and are found prominently in cancers. In wild type Ras-GTP, an allosteric switch promotes disorder to order transition in switch II, placing Gln(61) in the active site. We show that the "on" and "off" conformations of the allosteric switch can also be attained in RasG12V and RasQ61L. Although both mutants have similarly impaired active sites in the on state, RasQ61L stabilizes an anti-catalytic conformation of switch II in the off state of the allosteric switch when bound to Raf. This translates into more potent activation of the MAPK pathway involving Ras, Raf kinase, MEK, and ERK (Ras/Raf/MEK/ERK) in cells transfected with RasQ61L relative to RasG12V. This differential is not observed in the Raf-independent pathway involving Ras, phosphoinositide 3-kinase (PI3K), and Akt (Ras/PI3K/Akt). Using a combination of structural analysis, hydrolysis rates, and experiments in NIH-3T3 cells, we link the allosteric switch to the control of signaling in the Ras/Raf/MEK/ERK pathway, supporting a GTPase-activating protein-independent model for duration of the Ras-Raf complex.
Indexed as
Identifiers
What OpenQuestion holds
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.