ArticleOncotarget2016
Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Glucosamine links hyperglycemia to mTORC1 activation and glucose toxicity in diabetes.JCI insight · 2026Article
- Motif-guided identification of KRAS-interacting proteins.BMC biology · 2024Article
- The mTOR pathway controls phosphorylation of BRAF at T401.Cell communication and signaling : CCS · 2024Article
- BRAFScience advances · 2023Article
- The E3/E4 ubiquitin ligase UFD-2 suppresses normal and oncogenic signaling mediated by a Raf ortholog inScience signaling · 2023Article
- TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1.The Journal of cell biology · 2023Article
- Article
- Peptide-tiling screens of cancer drivers reveal oncogenic protein domains and associated peptide inhibitors.Cell systems · 2021Article
- Integrated in silico MS-based phosphoproteomics and network enrichment analysis of RASopathy proteins.Orphanet journal of rare diseases · 2021Article
- The Ins and Outs of RAS Effector Complexes.Biomolecules · 2021Review
- Review
- Review
- Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains.Oncogene · 2020Article
- Endogenous IQGAP1 and IQGAP3 do not functionally interact with Ras.Scientific reports · 2019Article
- Ras-Mediated Activation of the Raf Family Kinases.Cold Spring Harbor perspectives in medicine · 2019Review
- Nuclear localized Raf1 isoform alters DNA-dependent protein kinase activity and the DNA damage response.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Alterations of mTOR signaling impact metabolic stress resistance in colorectal carcinomas with BRAF and KRAS mutations.Scientific reports · 2018Article
- Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition.The EMBO journal · 2017Article
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK-pathway and a pharmacological target of growing clinical relevance, in particular in oncology. To understand how B-Raf itself is regulated, we combined mass spectrometry with genetic approaches to map its interactome in MCF-10A cells as well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1 double deficient DT40 lymphoma cells complemented with wildtype or mutant B-Raf expression vectors. Using a multi-protease digestion approach, we identified a novel ubiquitination site and provide a detailed B-Raf phospho-map. Importantly, we identify two evolutionary conserved phosphorylation clusters around T401 and S419 in the B-Raf hinge region. SILAC labelling and genetic/biochemical follow-up revealed that these clusters are phosphorylated in the contexts of oncogenic Ras, sorafenib induced Raf dimerization and in the background of the V600E mutation. We further show that the vemurafenib sensitive phosphorylation of the T401 cluster occurs in trans within a Raf dimer. Substitution of the Ser/Thr-residues of this cluster by alanine residues enhances the transforming potential of B-Raf, indicating that these phosphorylation sites suppress its signaling output. Moreover, several B-Raf phosphorylation sites, including T401 and S419, are somatically mutated in tumors, further illustrating the importance of phosphorylation for the regulation of this kinase.
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