ArticleMolecular and cellular biology2007
Differential regulation of B-raf isoforms by phosphorylation and autoinhibitory mechanisms.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.Cancer cell international · 2024Review
- 1,3-Dichloroadamantyl-Containing Ureas as Potential Triple Inhibitors of Soluble Epoxide Hydrolase, p38 MAPK and c-Raf.International journal of molecular sciences · 2023Article
- Cell cycle control by the insulin-like growth factor signal: at the crossroad between cell growth and mitotic regulation.Cell cycle (Georgetown, Tex.) · 2023Review
- HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation.Nature communications · 2022Article
- MITF activity is regulated by a direct interaction with RAF proteins in melanoma cells.Communications biology · 2022Article
- Role of serine 365 in BRAF V600E sensitivity to RAF inhibition.Pigment cell & melanoma research · 2021Article
- Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition.The EMBO journal · 2017Article
- Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles.Oncotarget · 2016Article
- Article
- Ras-mutant cancer cells display B-Raf binding to Ras that activates extracellular signal-regulated kinase and is inhibited by protein kinase A phosphorylation.The Journal of biological chemistry · 2013Article
- Function of alternative splicing.Gene · 2013Review
- Alternative splicing in oncogenic kinases: from physiological functions to cancer.Journal of nucleic acids · 2012Article
- IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload.Cardiovascular research · 2011Article
- Raf family kinases: old dogs have learned new tricks.Genes & cancer · 2011Article
- Article
- Impact of feedback phosphorylation and Raf heterodimerization on normal and mutant B-Raf signaling.Molecular and cellular biology · 2010Article
- Characterization and performance of nucleic acid nanoparticles combined with protamine and gold.Biomaterials · 2009Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The B-Raf proto-oncogene encodes several isoforms resulting from alternative splicing in the hinge region upstream of the kinase domain. The presence of exon 8b in the B2-Raf(8b) isoform and exon 9b in the B3-Raf(9b) isoform differentially regulates B-Raf by decreasing and increasing MEK activating and oncogenic activities, respectively. Using different cell systems, we investigated here the molecular basis of this regulation. We show that exons 8b and 9b interfere with the ability of the B-Raf N-terminal region to interact with and inhibit the C-terminal kinase domain, thus modulating the autoinhibition mechanism in an opposite manner. Exons 8b and 9b are flanked by two residues reported to down-regulate B-Raf activity upon phosphorylation. The S365A mutation increased the activity of all B-Raf isoforms, but the effect on B2-Raf(8b) was more pronounced. This was correlated to the high level of S365 phosphorylation in this isoform, whereas the B3-Raf(9b) isoform was poorly phosphorylated on this residue. In contrast, S429 was equally phosphorylated in all B-Raf isoforms, but the S429A mutation activated B2-Raf(8b), whereas it inhibited B3-Raf(9b). These results indicate that phosphorylation on both S365 and S429 participate in the differential regulation of B-Raf isoforms through distinct mechanisms. Finally, we show that autoinhibition and phosphorylation represent independent but convergent mechanisms accounting for B-Raf regulation by alternative splicing.
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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.