Figure 1

Topological scheme of modeled cyclic nucleotide signaling pathways. Main components of cyclic nucleotide signaling pathways and their cross-talk and downstream effects are depicted: Major signaling components of the simplified cAMP signaling pathway are shown in yellow, pivotal components of cGMP signaling in green and the three central cyclic nucleotide degrading phosphodiesterases (PDEs) are depicted in blue. Both, cAMP and cGMP signaling share in downstream effects on VASP (brown), which is phosphorylated at both, Ser157 and Ser239 differentially upon cyclic nucleotide dependent activation of their corresponding protein kinases (PKA, PKG). Levels of cAMP and cGMP react sensitively to pathway modulating compounds such as inhibitors of PDEs (Cilostamide, Milrinone) as well as adenylyl cyclase (AC) stimulating drugs (Iloprost, Forskolin) shown in red rectangles. This direct activation (green dashed arrow) and/or inhibition (red arrow) leads to an elevated cAMP level which subsequently feeds back on PDE3 (positive feedback) as well as on AC (negative feedback), as indicated by bold green and red colored arrows.