Figure 1.

Overview of compartmentalization of cAMP signalling. G_s-protein coupled receptors are stimulated by their appropriate ligands such as β₂-agonists and prostanoids. Subsequently, activation of adenylyl cyclase (AC) will lead to the production of the second messenger cyclic AMP (cAMP), whereas cAMP-specific phosphodiesterases (PDEs) will shape the cAMP gradient throughout the cell. Alternatively, AC can be directly activated by the cell membrane-permeable diterpene forskolin from the Indian plant Coleus forskolhlii. Elevation of cellular cAMP will simultaneously induce the activation of protein kinase A (PKA) and of the exchange protein directly activated by cAMP (Epac). Members of the A-kinase anchoring protein (AKAP) family will support the maintenance of cAMP compartmentalization upon binding to the cAMP-producing receptors, the cAMP effectors PKA and/or Epac as well as PDEs. The generation of cAMP-sensing multiprotein complexes by AKAPs is of tremendous importance to maintain spatio-temporal cAMP signalling at specific and discrete locations within the cell to regulate specific cellular responses upon signalling to several distinct effector proteins including vasodilator-stimulated phosphoprotein (VASP), a subset of small GTPases, and phospholipase C-ε (PLC-ε). Shown are tools being used to study the functioning of the cAMP-sensing multiprotein complexes: st-Ht31, the PKA binding blocking peptide known to act as a generic AKAP inhibitor [14,15,16]; 8-pCPT-2'-O-Me-cAMP and/or Sp-8-pCPT-2'-O-Me-cAMP, activator of Epac; 6-Bnz-cAMP, activator of PKA; Rp-8-CPT-cAMP, Rp-cAMPs, Rp-8-Bromo-cAMPs inhibitors of PKA.