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Logo of arthresbiomed central web sitesearch.manuscript submission.see also journal with issn 1478-6354registration.reference to the article.journal front page.
Arthritis Res. 2001; 3(Suppl A): P042.
Published online Jan 26, 2001. doi:  10.1186/ar211
PMCID: PMC3273187
The RIIbeta-subunit of protein kinase A (PKA) inhibits c-fos synthesis in T cells
N Mishra,1 M Tolnay,2 MR Elliott,1 DR Brown,1 GC Tsokos,2 and GM Kammer1
1Wake Forest University School of Medicine, Winston Salem, NC
2Walter Reed Army Institute, Silver Spring, MD, USA
21st European Workshop for Rheumatology Research
21st European Workshop for Rheumatology Research
1-4 March 2001
Vienna, Austria
Received January 15, 2001
In human primary T cells, the type II isozyme of protein kinase A (PKA-II) is localized to cytoskeletal elements or organelle membranes. Stimulation of T cells via the T cell receptor/CD3 complex or by addition of the cAMP analog, 8-Cl-cAMP, activates PKA-II, resulting in nuclear translocation of the RIIbeta-subunit from the cytosol and apparent RIIbeta DNA-binding. In current experiments, we demonstrated that recombinant RIIbeta forms a heterodimer with recombinant CREB, a nuclear transcription factor, as shown both by EMSA and immunoprecipitation/ immunoblotting. We found no evidence of direct binding of RIIb to c-fos-defined CRE oligonucleotides by EMSA. Although the RIIbeta-CREB heterodimer binds to the c-fos cAMP response element (CRE), phosphorylation of both RIIbeta and CREB by PKA enhances binding to c-fos CRE oligos. In vivo, phorbol myristate acetate (PMA)-induced synthesis of c-Fos protein is inhibited by DNA-binding of RIIbeta-CREB complexes. Taken together, these data suggest that, in addition to its primary function as an inhibitor of catalytic-subunit activity, the RIIbeta-subunit also acts as a transcription factor that can modulate the activity of the c-fos promoter. Therefore, we propose that RIIbeta may be a transcriptional repressor of c-fos.
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