ArticleNature2018
MEK drives BRAF activation through allosteric control of KSR proteins.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 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
85 citing papers in PubMed, 153 citations in OpenAlex.
- Langerhans cell histiocytosis: molecular mechanisms underlying pathogenesis and emerging targeted therapeutics.Cancer metastasis reviews · 2026Review
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A conserved dimerization element is required for protein kinase activation bybioRxiv : the preprint server for biology · 2026Article
- Dual RAF inhibition outperforms RAF-MEK combinations for suppressing ERK signaling in KRAS mutant cells.NPJ systems biology and applications · 2026Article
- MAPK Pathway Inhibition Reshapes Kinase Chemical Probe Reactivity Reflecting Cellular Activation States.ACS bio & med chem Au · 2026Article
- Identification and characterization of BRAF⇔TP53 interactions in melanoma.Cell reports · 2026Article
- Phosphoregulation of the novel hemi-arrestin MAPK scaffold Sms1 prevents untimely mating.Nature communications · 2026Article
- ZAK kinase at the crossroads of cellular stress: functional plasticity, human pathobiology, and precision therapeutics.Frontiers in cell and developmental biology · 2026Review
- The BRAF-specific region suppresses cysteine-rich domain-lipid interaction independently of canonical autoinhibition by the 14-3-3 dimer.Protein science : a publication of the Protein Society · 2026Article
- Kinase suppressor of Ras 1 (KSR1) promotes liver carcinogenesis via activation of the RAS/RAF/MEK/ERK signaling pathway.JHEP reports : innovation in hepatology · 2025Article
- Targeting Kinase Suppressor of Ras 1 (KSR1) for Cancer Therapy.Pharmaceutics · 2025Review
- Single-molecule imaging quantifies oncogenic KRAS dynamics for enhanced accuracy of therapeutic efficacy assessment.iScience · 2025Article
- Kinase signaling cascades: an updated mechanistic landscape.Chemical science · 2025Review
- A Proteomics Outlook on the Molecular Effectors of CAR-T Cell Therapy in Cancer Management.Journal of proteome research · 2025Review
- Plasma proteomic profiling of hospitalized patients co-infected with HIV and SARS-CoV-2.Frontiers in immunology · 2025Article
- Novel Ser74 of NF-κB/IκBα phosphorylated by MAPK/ERK regulates temperature adaptation in oysters.Cell communication and signaling : CCS · 2024Article
- The Raf/LIN-45 C-terminal distal tail segment negatively regulates signaling in Caenorhabditis elegans.Genetics · 2024Article
- Enzyme Is the Name-Adapter Is the Game.Cells · 2024Review
- MAPK/ERK-PK(Ser11) pathway regulates divergent thermal metabolism of two congeneric oyster species.iScience · 2024Article
- Transposase-assisted tagmentation: an economical and scalable strategy for single-worm whole-genome sequencing.G3 (Bethesda, Md.) · 2024Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
RAF family kinases have prominent roles in cancer. Their activation is dependent on dimerization of their kinase domains, which has emerged as a hindrance for drug development. In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK). Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. Although GTP-bound RAS can modulate the dimerization of RAF isoforms by engaging their RAS-binding domains, KSR1 and KSR2 lack an RAS-binding domain and therefore the regulatory principles underlying their dimerization with other RAF family members remain unknown. Here we show that the selective heterodimerization of BRAF with KSR1 is specified by direct contacts between the amino-terminal regulatory regions of each protein, comprising in part a novel domain called BRS in BRAF and the coiled-coil-sterile α motif (CC-SAM) domain in KSR1. We also discovered that MEK binding to the kinase domain of KSR1 asymmetrically drives BRAF-KSR1 heterodimerization, resulting in the concomitant stimulation of BRAF catalytic activity towards free MEK molecules. These findings demonstrate that KSR-MEK complexes allosterically activate BRAF through the action of N-terminal regulatory region and kinase domain contacts and challenge the accepted role of KSR as a scaffold for MEK recruitment to RAF.
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.