Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.

By P. Wan, Mathew J. Garnett, S. Roe, Sharlene Lee, D. Niculescu-Duvaz, V. Good, Cancer Genome Project, C.Michael Jones, Christopher J. Marshall, Caroline J. Springer and 2 more. 2004

2,727 citations recorded by the source corpus.

Subfields: Molecular Biology

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In Molecular Biology

1. Feng Zhang
2. Walter Kolch
3. C. Der
4. P. Roberts
5. Neville E. Sanjana
6. Junying Yuan
7. M. McKay
8. DK Morrison

Citations in the corpus

• Quantitative missense variant effect prediction using large-scale mutagenesis data (2017, neutral): “For example, both gain- and loss-of-function variants of BRAF can be pathogenic (Rodriguez-Viciana et al., 2006; Wan et al., 2004).”
• Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF (2013, neutral): “…the substitution of valine at position 600 by glutamic acid (BRAF V600E) that results in the constitutive activation of its serine/threonine kinase activity and sustained activation of the mitogen-activated protein kinase (MAPK) signal transduction pathway (Davies et al., 2002; Wan et al., 2004).”
• Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. (2005, background): “A similar mutation (D594V) has been shown to lead to impaired kinase activity of BRAF and loss of the ability to activate extracellular signal-regulated kinase (21).”
• BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis (2004, background): “complex with both wt and oncogenic V599E BRAF kinase (33).”
• Glioma Subclassifications and Their Clinical Significance (2017, background): “BRAF is a serine/threonine protein kinase that plays an integral role in cell differentiation, growth, and proliferation through its role in the Ras/Raf/MEK/extracellular regulated kinase pathway [99, 100].”
• Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. (2011, background): “Preclinical data demonstrate that both the V600E and G469A mutation are associated with increased BRAF kinase activity and downstream ERK1/2 phosphorylation.(9) D594G mutants may have, in contrast, lower kinase activity.”
• Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma (2013, neutral): “Another new BRAF alteration was identified in ICGC_PA65, resulting in a three-amino-acid insertion (p.Arg506_insValLeuArg, insVLR) in the interdomain cleft of BRAF—a structural region linked to BRAF activity 17 and homodimerization 18 .”
• RAF inhibitors transactivate RAF dimers and ERK signaling in cells with wild-type BRAF (2010, neutral): “A side-to-side dimer of the kinase domain is observed in crystal structures of BRAF 11 , and the residues at the dimer interface are conserved in all RAF isoforms.”
• Chemokine signaling via the CXCR2 receptor reinforces senescence. (2008, background): “Three independent experiments yielding equivalent results were performed. renders it constitutively active (Wan et al., 2004) and could induce OIS.”
• The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches (2012, background): “On the other hand, the activated BRAF mutants signal to MEK directly [25].”
• HSP90 at the hub of protein homeostasis: emerging mechanistic insights (2010, background): “Similarly, the most common activating mutation in BRAF, Val600Glu, renders the inactive conformation energetically unfavourabl”
• Integrating signals from RTKs to ERK/MAPK (2007, background): “However, it was not until kinase-impaired, oncogenic B-Raf proteins were found to activate ERK through the binding and transactivation of C-Raf that the significance of Raf heterodimerization was fully appreciated (Wan et al., 2004).”