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. 2013 Oct;55(3-4):247-52.
doi: 10.1016/j.molimm.2013.02.001. Epub 2013 Mar 19.

BRAF splice variants in rheumatoid arthritis synovial fibroblasts activate MAPK through CRAF

Richard H Weisbart  1 , Grace Chan, Erica Li, Niloofar Farmani, Emil Heinze, Antonia Rubell, Robert N Nishimura, Keith Colburn
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BRAF splice variants in rheumatoid arthritis synovial fibroblasts activate MAPK through CRAF

Richard H Weisbart et al. Mol Immunol. 2013 Oct.

Abstract

Rheumatoid arthritis (RA) is a destructive polyarthritis in which synovial-like fibroblasts (SFs) invade and erode cartilage by expressing membrane-anchored type 1 matrix metalloproteinase (MT1-MMP). The mitogen activated protein kinase (MAPK) pathway is activated in RA SFs, but the mechanism of activation is unknown. Here we identify aberrant BRAF splice variants with deletions in both the kinase domain and RAS-binding domain (RBD) in SFs from the majority of RA patients and show that these BRAF splice variants constitutively activate MAPK through CRAF, increase expression of MT1-MMP, and enhance fibroblast invasion of collagen.

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