Fig 1.

Interaction of PDE4 with cellular proteins. The activity of PDE4 is regulated by both extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and protein kinase A (PKA). ERK1/2 exerts an inhibitory effect on the activity of long form PDE4s and a stimulatory effect on hydrolytic activity of short form PDE4s, while phosphorylation of long PDE4 isoforms by PKA leads to an increase in their activity in cells. Under different conditions, PDE4 exerts diverse biological functions through interacting with multiple proteins. For example, PDE4 interacts with DNA-PKs and thus regulates cell death. PDE4 binds to A-kinase-anchoring proteins (AKAPs) and modulates T cell activation. In addition, interaction of PDE4 with disrupted in schizophrenia 1 (DISC1) is involved in the process of mental disorders, such as schizophrenia.