Downregulation of CIITA Function by Protein Kinase A (PKA)-Mediated Phosphorylation: Mechanism of Prostaglandin E, Cyclic AMP, and PKA Inhibition of Class II Major Histocompatibility Complex Expression in Monocytic Lines
Copyright policy )Downregulation of CIITA Function by Protein Kinase A (PKA)-Mediated Phosphorylation: Mechanism of Prostaglandin E, Cyclic AMP, and PKA Inhibition of Class II Major Histocompatibility Complex Expression in Monocytic Lines
Prostaglandins, pleiotropic immune modulators that induce protein kinase A (PKA), inhibit gamma interferon induction of class II major histocompatibility complex (MHC) genes. We show that phosphorylation of CIITA by PKA accounts for this inhibition. Treatment with prostaglandin E or 8-bromo-cyclic AMP or transfection with PKA inhibits the activity of CIITA in both mouse and human monocytic cell lines. This inhibition is independent of other transcription factors for the class II MHC promoter. These same treatments also greatly reduced the induction of class II MHC mRNA by CIITA. PKA phosphorylation sites were identified using site-directed mutagenesis and phosphoamino acid analysis. Phosphorylation at CIITA serines 834 and 1050 accounts for the inhibitory effects of PKA on CIITA-driven class II MHC transcription. This is the first demonstration that the posttranslational modification of CIITA mediates inhibition of class II MHC transcription.
- UNC Lineberger Comprehensive Cancer Center United States
- University of North Carolina at Chapel Hill United States
Histocompatibility Antigens Class II, 8-Bromo Cyclic Adenosine Monophosphate, Down-Regulation, Nuclear Proteins, Cyclic AMP-Dependent Protein Kinases, Dinoprostone, Monocytes, Cell Line, Mice, Cyclic AMP, Trans-Activators, Animals, Humans, Alprostadil, Phosphorylation, Phosphoamino Acids
Histocompatibility Antigens Class II, 8-Bromo Cyclic Adenosine Monophosphate, Down-Regulation, Nuclear Proteins, Cyclic AMP-Dependent Protein Kinases, Dinoprostone, Monocytes, Cell Line, Mice, Cyclic AMP, Trans-Activators, Animals, Humans, Alprostadil, Phosphorylation, Phosphoamino Acids
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