To investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRbeta(1) (*)0401, (*)0402, (*)0403 and (*)0404 subtypes on protein kinase A (PKA) signaling.
To detect the activities of adenylate cyclase (AC), cAMP and PKA in transfectants expressing rheumatoid arthritis-associated HLA-DRbeta(1) subtypes and their mutants.
The levels of AC, cAMP and PKA of HLA-DRbeta(1) (*)0401 and (*)0404 transfectants were significant lower than that of HLA-DRbeta(1) (*)0402 and (*)0403 transfectants (P < 0.01). The mutant HLA-DRbeta(1) (*)0403 transfectants expressing DRRAE or QRRAA secreted lower levels of PKA, cAMP and AC (P < 0.01).
RA-associated HLA-DRbeta(1) (*)0401 and (*)0404 expression suppressed intracellular PKA signaling pathway, and may mediate abnormal intracellular signaling in rheumatoid arthritis.