Activation of PDE2 and PDE5 by specific GAF ligands: delayed activation of PDE5.

ABSTRACT:

Background and purpose

By controlling intracellular cyclic nucleotide levels, phosphodiesterases (PDE) serve important functions within various signalling pathways. The PDE2 and PDE5 families are allosterically activated by their substrate cGMP via regulatory so-called GAF domains. Here, we set out to identify synthetic ligands for the GAF domains of PDE2 and PDE5.

Experimental approach

Using fluorophore-tagged, isolated GAF domains of PDE2 and PDE5, promising cGMP analogues were selected. Subsequently, the effects of these analogues on the enzymatic activity of PDE2 and PDE5 were analysed.

Key results

The PDE2 ligands identified, 5,6-DM-cBIMP and 5,6-DCl-cBIMP, caused pronounced, up to 40-fold increases of the cAMP- and cGMP-hydrolysing activities of PDE2. The ligand

SUBMITTER: Jager R 

PROVIDER: S-EPMC3010573 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature