Retinoylation of the type II cAMP-binding regulatory subunit of cAMP-dependent protein kinase is increased in psoriatic human fibroblasts.
Previously, we have reported a defect in the cAMP-dependent protein kinases (cAMP-PK) in psoriatic cells (i.e., a decrease in 8-azido-[32P]cAMP binding to the regulatory subunits and a decrease in phosphotransferase activity) which is rapidly reversed with retinoic acid (RA) treatment of these cells. This led us to examine a possible direct interaction between retinoids and the RI and RII regulatory subunits through retinoylation. Retinoylation of RI and RII present in normal and psoriatic human fibroblasts was analysed by [3H]RA treatment of these cells, followed either by chromatographic separation of the regulatory subunits or by their specific immunoprecipitation. These studies indicated that RI and RII can be retinoylated. [3H]RA labeling of the RII subunit was significantly (P < 0.005) greater in psoriatic fibroblasts (nine subjects; mean 7.47 relative units +/- 1.37 SEM) compared to normal fibroblasts (eight subjects; mean 2.46 relative +/- 0.49 SEM). [3H]RA labeling of and the increase in 8-azido-[32P]-binding to the RI and RII subunit in psoriatic fibroblasts showed a similar time course. This suggests that the rapid effect of retinoic acid treatment to enhance 8-azido-[32P]-cAMP binding to the RI and RII in psoriatic fibroblasts may be due, in part, to covalent modification of the regulatory subunits by retinoylation.
Tournier
S
S
Unité INSERM 427, Faculté des Siences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.
Raynaud
F
F
Gerbaud
P
P
Lohmann
S M
SM
Anderson
W B
WB
Evain-Brion
D
D
D000345:Affinity Labels; D001345:Autoradiography; D001386:Azides; D015153:Blotting, Western; D002458:Cell Fractionation; D002845:Chromatography; D000242:Cyclic AMP / Q000031:analogs & derivatives; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D010761:Phosphorus Radioisotopes; D011485:Protein Binding / Q000502:physiology; D011565:Psoriasis / Q000201:enzymology*; D012867:Skin / Q000166:cytology / Q000187:drug effects; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D014316:Tritium
D000345:Affinity Labels; D001386:Azides; D010761:Phosphorus Radioisotopes; D014316:Tritium; C017042:8-azidoadenosine-3',5'-monophosphate; D014212:Tretinoin; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases