GAF domain-induced activation of phosphodiesterases 2 and 5

The second messenger cGMP is involved in several physiological functions such as smooth muscle relaxation and inhibition of platelet aggregation. Besides cGMP synthesis, hydrolysis of cGMP by cyclic nucleotide phosphodiesterases (PDEs) determines the shape of cGMP signals. Eleven PDE families are known differing in regulation and cAMP/cGMP specificity. PDEs are homodimers; each monomer being composed of different N-terminal regulatory domains and a C-terminal catalytic domain highly conserved between the PDE families. Five PDEs contain a tandem of so called GAF domains in their N termini that have been shown to bind cGMP or cAMP. At least in PDEs 2, 5 and 6, binding of cGMP to the GAF domains leads to stimulation of the enzymes. Here, we focussed on the GAF-mediated stimulation of PDEs 2 and 5.