ABSTRACT
The phosphodiesterase 4 (PDE4) enzymes, also termed 3',5'-cyclic adenosine monophosphate (cAMP)-specific phosphodiesterases or high-affinity cAMP PDEs, specifically hydrolyze cAMP with high affinity and are the targets for a class of drugs with antidepressant, memory-enhancing, anti-inflammatory, and immunomodulatory functions. An important practical question is how studies on the cellular regulation of PDE4 isoforms should influence drug development. The identification of Upstream Conserved Region 1 and 2 as intrinsic components of PDE4 proteins posed a number of interesting questions about their role in PDE4 function. The interaction of PDE4 proteins with molecular chaperones and other proteins that modulate protein folding in cells, such as immunophilins, has the potential to influence diverse aspects of PDE4 function. One of the most noteworthy aspects of the PDE4A5–XAP2 interaction is that it directly changes several enzymatic and pharmacological characteristics of PDE4A5. The SH3-domain-containing proteins SRC, FYN, and LYN interact with human PDE4A4 and its rat homologue, PDE4A5.
