Impact of rheumatoid arthritis-associated HLA-DRbeta1 subtypes on protein kinase A signaling.
OBJECTIVE
To investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRbeta1 * 0401, * 0402, * 0403, * 0404 and * 0101 subtypes on the protein kinase A (PKA) signaling pathway.


METHODS
Adenylate cyclase (AC), cAMP and PKA activity in transfectants expressing RA-associated HLA-DRbeta1 subtypes and their mutants were detected.


RESULTS
Compared to HLA-DRbeta1 * 0402 transfectants, the RA-associated HLA-DRbeta1 * 0401, * 0404 and * 0101 transfectants produced significantly lower levels of AC, cAMP and PKA.


CONCLUSIONS
RA-associated HLA-DRbeta1 molecules are involved in the pathogenesis of RA through down-regulation of the PKA signaling pathway.
Li
Zhanguo
Z
Department of Rheumatology and Immunology, People's Hospital, Beijing University Medical School, Beijing 100034, China. zgli98@yahoo.com
Han
Lei
L
Jia
Rulin
R
Li
Jing
J
D000262:Adenylyl Cyclases / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D000242:Cyclic AMP / Q000032:analysis / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D015536:Down-Regulation; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics*; D016130:Immunophenotyping; D066298:In Vitro Techniques; D015398:Signal Transduction
D006684:HLA-DR Antigens; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases