FIGURE 2.

The cAMP signaling pathways. The well-known, “old” second messenger cAMP is generated upon activation of G_s-coupled receptors (such as the β-adrenoceptors) and subsequent stimulation of a diverse subset of adenylyl cyclases (ACs), shown are the transmembrane ACs (tmACs) and the soluble ACs (sACs). cAMP exerts its effects through its primary effector protein kinase A (PKA), next to the exchange protein directly activated by cAMP (Epac) cyclic nucleotide-gated channels (HCN) and Popeye domain containing (POPDC) proteins (Brand, 2018; Robichaux and Xiaodong Cheng, 2018). The multifaceted signaling properties of cAMP are controlled by A-kinase anchoring proteins (AKAPs) and phosphodiesterases (PDEs), enabling cAMP signaling in space and time (Schmidt et al., 2013; Poppinga et al., 2014; Han et al., 2015). For further details, see text.