PKA activity also significantly affects cytoplasmic potassium concentration within T cells by inhibiting the activity of Kv1.3 (187) and KCa3.1 (188, 189), channels which are responsible for the bulk of potassium efflux by T cells (190). In a negative-feedback fashion, PKA induces reduction of the cytosolic cAMP concentration by directly phosphorylating AC6 in an inhibitory fashion (191) as well as isoforms of PDE3 (192), PDE4 (193, 194), PDE8A (195) in a stimulatory manner. At the transcriptional level, PKA augments the activity of CREB cAMP responsive element binding (CREB), cAMP responsive element modulator (CREM) and activating transcription factor-1 (ATF-1) (196), which induce or counteract the transcription of multiple inflammation-relevant genes such as IL-2 (197–199), IFNγ (200–202), IL-4 and IL-13 (203, 204), IL-17 (205–208), and FoxP3 (209, 210). Specifically, PKA promotes the transcriptional activity of CREB by phosphorylating it thus increasing its affinity for its co-activators CBP and p300 (211), and by promoting the nuclear localization of CRTC (212), another family of CREB co-activators. Finally, PKA directly phosphorylates and activates ATF-1 (213) as well as distinct CREM isoforms (214) in a way similar to CREB.