类风湿关节炎共同表位QK/RRAA对蛋白激酶A通路的抑制作用

摘要

Objective　To study the effect of rheumatoid arthritis (RA) shared epitope on protein kinase A (PKA) signaling.Methods　The activities of adenylate cyclase (AC),cAMP and PKA in transfectants expressing RA shared epitope and their mutants were determined.Results　HLA-DRβ10404 transfectant produced a significant lower levels of AC,cAMP and PKA compared with HLA-DRβ10403 transfectants (P＜0.01).Positions 70 and 74 of DRβ10404 sequence QRRAA were critical in PKA signaling.Conclusion　RA shared epitope suppresses PKA signaling.Q70 and A74 are the key residues in PKA signal transduction and may mediate abnormal intracellular signaling in RA.%目的研究类风湿关节炎(RA)共同表位QK/RRAA及其变异对细胞内蛋白激酶A(PKA)信号通路的影响。方法测定HLA-DRβ10404及其变异体转基因细胞内PKA、cAMP及腺苷环化酶(AC)的浓度及活性。结果 HLA-DRβ10404转基因细胞的PKA活力、cAMP水平及AC活力明显低于HLA-DRβ10403转基因细胞株(P＜0.01)。HLA-DRβ10404序列第70～74位氨基酸QRRAA中的Q70及A74是抑制PKA信号通路的关键氨基酸。结论类风湿关节炎共同表位QK/RRAA的表达可抑制PKA、cAMP和AC的活性，并由此参与类风湿关节炎的发病。