[Effect of rheumatoid arthritis associated HLA-DRbeta1 subtypes on protein kinase A signaling].
OBJECTIVE
To investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRbeta(1) (*)0401, (*)0402, (*)0403 and (*)0404 subtypes on protein kinase A (PKA) signaling.


METHODS
To detect the activities of adenylate cyclase (AC), cAMP and PKA in transfectants expressing rheumatoid arthritis-associated HLA-DRbeta(1) subtypes and their mutants.


RESULTS
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).


CONCLUSIONS
RA-associated HLA-DRbeta(1) (*)0401 and (*)0404 expression suppressed intracellular PKA signaling pathway, and may mediate abnormal intracellular signaling in rheumatoid arthritis.
Li
Z
Z
Department of Rheumatology and Immunology, People's Hospital, Beijing Medical University, Beijing 100034, China.
Xiao
L
L
Jia
R
R
Joseph
H
H
D000262:Adenylyl Cyclases / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D015398:Signal Transduction; D019076:Transgenes
D006684:HLA-DR Antigens; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases