Stimulation of PDE2 by the GAF domain ligands 5,6-DM-cBIMP and 5,6-DCI-cBIMP. PDE activity was measured in cytosolic fractions of PDE2 overexpressing HEK cells in the presence of increasing concentrations of 5,6-DM-cBIMP (A, D), 5,6-DCI-cBIMP (B, E) or cGMP (C) at the indicated concentrations of cAMP (A–C) and cGMP (D–E) as substrate. The reactions were carried out in 5 min incubations as described in detail in Methods. Data shown are mean ± SD of at least three independent experiments performed in duplicate.