Autophosphorylation on S614 inhibits the activity and the transforming potential of BRAF

Title: Autophosphorylation on S614 inhibits the activity and the transforming potential of BRAF
Authors: Dernayka, Layal
Rauch, Nora
Jarboui, Mohamed-Ali
Zebisch, Armin
Romano, David
Von Kriegsheim, Alex
Kolch, Walter
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Date: Sep-2016
Online since: 2019-04-01T12:12:14Z
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.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Journal: Cellular Signalling
Volume: 28
Issue: 9
Start page: 1432
End page: 1439
Copyright (published version): 2016 Elsevier
Keywords: BRAFInhibition of kinase activity and transformationS614 autophosphorylation
DOI: 10.1016/j.cellsig.2016.06.016
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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