Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Dernayka, L; Rauch, N; Jarboui, MA; Zebisch, A; Texier, Y; Horn, N; Romano, D; Gloeckner, CJ; Kriegsheim, Av; Ueffing, M; Kolch, W; Boldt, K.
Autophosphorylation on S614 inhibits the activity and the transforming potential of BRAF.
Cell Signal. 2016; 28(9):1432-1439
Doi: 10.1016/j.cellsig.2016.06.016
Web of Science
PubMed
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- Zebisch Armin
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- Abstract:
- The BRAF proto-oncogene serine/threonine-protein kinase, known as BRAF, belongs to the RAF kinase family. It regulates the MAPK/ERK signalling pathway affecting several cellular processes such as growth, survival, differentiation, and cellular transformation. BRAF is mutated in ~8% of all human cancers with the V600E mutation constituting ~90% of mutations. Here, we have used quantitative mass spectrometry to map and compare phosphorylation site patterns between BRAF and BRAF V600E. We identified sites that are shared as well as several quantitative differences in phosphorylation abundance. The highest difference is phosphorylation of S614 in the activation loop which is ~5fold enhanced in BRAF V600E. Mutation of S614 increases the kinase activity of both BRAF and BRAF V600E and the transforming ability of BRAF V600E. The phosphorylation of S614 is mitogen inducible and the result of autophosphorylation. These data suggest that phosphorylation at this site is inhibitory, and part of the physiological shut-down mechanism of BRAF signalling. Copyright © 2016 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Animals -
- Cell Line -
- Cell Transformation, Neoplastic - metabolism
- Cell Transformation, Neoplastic - pathology
- Humans -
- Mice -
- Mitogen-Activated Protein Kinase Kinases - metabolism
- Mutation - genetics
- Phosphorylation -
- Phosphoserine - metabolism
- Protein Binding -
- Proto-Oncogene Proteins B-raf - chemistry
- Proto-Oncogene Proteins B-raf - metabolism
- Rats -
- Find related publications in this database (Keywords)
- BRAF
- S614 autophosphorylation
- Inhibition of kinase activity and transformation