Fig. 1.

Role of PDEs in regulation of signal transduction. In the model of the second messenger concept originally put forth by Sutherland and Rall (14), first messengers—such as hormones, neurotransmitters, cytokines, and growth factors—upon interacting with receptors on the cell surface, generate the production of a second messenger, such as cAMP, which then redirects the machinery of the cell, affecting many physiological processes. PDEs, by controlling the steady-state levels and temporal and spatial components of cAMP, are central to controlling and regulating this signal transduction. ATF-1, activating transcription factor-1; CREB, cAMP-response element binding protein; CREM, cAMP-response element modulator; Gs, stimulatory guanine nucleotide-binding protein; ICER, inducible cAMP early repressor protein; R, G protein-coupled metabotropic receptor. Reproduced with permission from ref. 4.