ArticleThe EMBO journal2016
Activation loop phosphorylation regulates B-Raf in vivo and transformation by B-Raf mutants.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- High-resolution measurement of ERK activation state reveals determinants of BRAF regulation and drug sensitivity.bioRxiv : the preprint server for biology · 2026Article
- Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns.PLoS computational biology · 2025Article
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- MOST wanted: navigating the MAPK-OIS-SASP-tumor microenvironment axis in primary pediatric low-grade glioma and preclinical models.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- Reversible control of kinase signaling through chemical-induced dephosphorylation.Communications biology · 2024Article
- An updated literature on BRAF inhibitors (2018-2023).Molecular diversity · 2024Review
- Enzyme Is the Name-Adapter Is the Game.Cells · 2024Review
- DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis.Cancers · 2024Article
- A review on potential heterocycles for the treatment of glioblastoma targeting receptor tyrosine kinases.Oncology research · 2024Review
- BRAFScience advances · 2023Article
- Analysis of RAS and drug induced homo- and heterodimerization of RAF and KSR1 proteins in living cells using split Nanoluc luciferase.Cell communication and signaling : CCS · 2023Article
- HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation.Nature communications · 2022Article
- The oncogenic fusion landscape in pediatric CNS neoplasms.Acta neuropathologica · 2022Review
- Spatially interacting phosphorylation sites and mutations in cancer.Nature communications · 2021Article
- BRAF mutation and its inhibitors in sarcoma treatment.Cancer medicine · 2020Review
- Review
- Review
- Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains.Oncogene · 2020Article
- B-Raf deficiency impairs tumor initiation and progression in a murine breast cancer model.Oncogene · 2019Article
- Does Ras Activate Raf and PI3K Allosterically?Frontiers in oncology · 2019Review
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17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite being mutated in cancer and RASopathies, the role of the activation segment (AS) has not been addressed for B-Raf signaling in vivo. Here, we generated a conditional knock-in mouse allowing the expression of the B-Raf(AVKA) mutant in which the AS phosphoacceptor sites T599 and S602 are replaced by alanine residues. Surprisingly, despite producing a kinase-impaired protein, the Braf(AVKA) allele does not phenocopy the lethality of Braf-knockout or paradoxically acting knock-in alleles. However, Braf(AVKA) mice display abnormalities in the hematopoietic system, a distinct facial morphology, reduced ERK pathway activity in the brain, and an abnormal gait. This phenotype suggests that maximum B-Raf activity is required for the proper development, function, and maintenance of certain cell populations. By establishing conditional murine embryonic fibroblast cultures, we further show that MEK/ERK phosphorylation and the immediate early gene response toward growth factors are impaired in the presence of B-Raf(AVKA). Importantly, alanine substitution of T599/S602 impairs the transformation potential of oncogenic non-V600E B-Raf mutants and a fusion protein, suggesting that blocking their phosphorylation could represent an alternative strategy to ATP-competitive inhibitors.
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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.