Abstract:
INTRODUCTION:BRAF (v raf murine sarcoma viral oncogene homologue B1) is a serine-threonine kinase involved in the mitogen-activated protein kinase (MAPK) signalling pathway, known to be implicated in the production of pro-inflammatory cytokines.We have observed that sera from rheumatoid arthritis (RA) patients recognize the BRAF's catalytic domain, which encompasses amino acids 416 to 766. Here, we identify peptide targets of anti-BRAF autoantibodies and test whether anti-BRAF autoantibodies may interfere with BRAF kinase activity. METHODS:Anti-BRAF autoantibodies were detected by ELISA (enzyme-linked immunosorbent assay) in the serum of RA patients and controls, using 40 overlapping 20mer peptides encompassing the catalytic domain of BRAF as immunosorbents. To test whether autoantibodies to BRAF influence BRAF kinase activity, we developed an in vitro phosphorylation assay of MEK1 (mitogen extracellular regulated kinase), a major BRAF substrate. MEK1 phosphorylation by BRAF was tested in the presence of purified anti-BRAF autoantibodies from RA patients or control antibody. RESULTS:We found that one BRAF peptide, P25 (656 to 675), is specifically recognized by autoantibodies from RA patients. Of interest, anti-P25 autoantibodies are detected in 21% of anti-CCP (cyclic citrullinated peptides) negative RA patients. Anti-BRAF autoantibodies activate the in vitro phosphorylation of MEK1 mediated by BRAF. CONCLUSIONS:Anti-BRAF autoantibodies from RA patients preferentially recognize one BRAF peptide: P25. Autoantibody responses to P25 are detected in 21% of anti-CCP negative RA patients. Most anti-BRAF autoantibodies activate BRAF kinase activity.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Charpin C,Martin M,Balandraud N,Roudier J,Auger Idoi
10.1186/ar3165subject
Has Abstractpub_date
2010-01-01 00:00:00pages
R194issue
5eissn
1478-6354issn
1478-6362pii
ar3165journal_volume
12pub_type
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journal_title:Arthritis research & therapy
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abstract:: ...
journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4101
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3911
更新日期:2012-07-12 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar1894
更新日期:2006-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3108
更新日期:2010-01-01 00:00:00
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doi:10.1186/s13075-017-1251-y
更新日期:2017-03-07 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
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journal_title:Arthritis research & therapy
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doi:10.1186/s13075-016-1128-5
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-016-1203-y
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0632-3
更新日期:2015-05-21 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2632
更新日期:2009-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3764
更新日期:2012-03-06 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02361-2
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2795
更新日期:2009-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 评论,社论
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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