title: Defective cAMP-dependent phosphorylation of intact T lymphocytes in active systemic lupus erythematosus.
abstract: The present study was undertaken to establish whether cAMP-dependent phosphorylation of endogenous substrates is impaired in T lymphocytes from subjects with active systemic lupus erythematosus (SLE). In normal human T lymphocytes, the cell-permeable cAMP analog, N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate, induced phosphorylation of substrates with molecular masses of 17.5, 23/25, 33.5 kDa on one-dimensional SDS/PAGE. Maximal phosphorylation occurred at 60 min. In contrast to healthy T cells, the extent of substrate phosphorylation achieved in active SLE T cells (n = 8) was only 15% at 60 min in the 17.5-kDa substrate, 21% in the 23/25-kDa substrate, and 9% in the 33.5-kDa substrate. The rheumatic disease controls (rheumatoid arthritis; primary Sjögren syndrome; n = 8) exhibited a mean 72%, 124%, and 85%, respectively, of phosphorylation observed in healthy T cells. Because the only known mechanism by which cAMP acts is via cAMP-dependent protein kinase (protein kinase A), these data raise the possibility of a defect at the level of this kinase in SLE T lymphocytes.
authors.affiliation: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
authors.forename: P
authors.initials: P
authors.lastname: Hasler
authors.forename: L A
authors.initials: LA
authors.lastname: Schultz
authors.forename: G M
authors.initials: GM
authors.lastname: Kammer
mesh_terms: D000328:Adult; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D012016:Reference Values; D012859:Sjogren's Syndrome / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D003994:Bucladesine; D000242:Cyclic AMP