Increased intracellular cyclic AMP levels block PKC-mediated T cell activation by inhibition of c-jun transcription.
Antigen binding to specific receptors on T cells (TCR) results in a rapid and transient phosphoinositide hydrolysis followed by activation of protein kinase C (PKC). Activators of adenylate cyclase or cell permeable cyclic AMP (cAMP) derivatives antagonize this effect and inhibit T cell activation by interfering with phosphoinositide turnover. We found that dibutyryl cAMP (dbcAMP) also affects intracellular event(s) remote from the phosphoinositide hydrolysis step. Thus, dbcAMP inhibits T cell activation by TPA + ionomycin which directly activate PKC and bypass the requirement for TCR perturbation. Under these conditions, dbcAMP was found to interfere with the TPA + ionomycin-mediated induction of c-jun encoding the JUN/AP-1 transcription factor. The data suggest that increased cAMP levels interfere with several activation steps in T cells including the induction of early activation genes possessing the consensus AP-1 recognition site.
Tamir
A
A
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University, Negev, Beer Sheva, Israel.
Isakov
N
N
D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D015759:Ionomycin; D003994:Bucladesine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate