TY - JOUR
T1 - BRAF splice variants in rheumatoid arthritis synovial fibroblasts activate MAPK through CRAF
AU - Weisbart, Richard H.
AU - Chan, Grace
AU - Li, Erica
AU - Farmani, Niloofar
AU - Heinze, Emil
AU - Rubell, Antonia
AU - Nishimura, Robert N.
AU - Colburn, Keith
N1 - Funding Information:
This work was sponsored by a grant from the Veterans Affairs .
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
KW - MAPK cascade
KW - Oncogene
KW - Rheumatoid arthritis
UR - http://www.scopus.com/inward/record.url?scp=84877604986&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877604986&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2013.02.001
DO - 10.1016/j.molimm.2013.02.001
M3 - Article
C2 - 23517740
SN - 0161-5890
VL - 55
SP - 247
EP - 252
JO - Molecular Immunology
JF - Molecular Immunology
IS - 3-4
ER -