POSTTRANSLATIONAL ABNORMALITY OF THE TYPE-II CYCLIC-AMP-DEPENDENT PROTEIN-KINASE IN PSORIASIS - MODULATION BY RETINOIC ACID

Previously, we have reported a decrease in the binding of a cAMP analo g to the regulatory subunits of cAMP-dependent protein kinase (cAMP-PK ), as well as a decrease in cAMP-PK activities, in psoriatic cells. Re tinoic acid (RA) treatment of these cells can induce an increase in cA MP-PK toward normal levels. To better define the effect of retinoic ac id on the cAMP-PK system in psoriatic fibroblasts, Western blot analys is using an RII alpha specific antibody and in vivo phosphorylation ex periments were carried out to determine possible changes in the RII re gulatory subunit. Our results indicate a decrease in the binding of th e cAMP analog 8-azido-[P-32]-cAMP with no change in the level of RII p rotein in psoriatic fibroblasts. In addition, by two-dimensional gel e lectrophoresis we observed the presence oi a phosphorylated Form of RI I unique to psoriatic cells which is suppressed by RA treatment. This study suggests an altered posttranslational modification of the cAMP-P KII in psoriatic fibroblasts which can be reversed by exposure of thes e cells to RA. (C) 1995 Wiley-Liss, Inc.