PDE4 associates with different scaffolding proteins: modulating interactions as treatment for certain diseases.
cAMP is an ubiquitous second messenger that is crucial to many cellular processes. The sole means of terminating the cAMP signal is degradation by cAMP phosphodiesterases (PDEs). The PDE4 family is of particular interest because PDE4 inhibitors have therapeutic potential for the treatment of various inflammatory and auto-immune diseases and also have anti-depressant and memory-enhancing effects. The subcellular targeting of PDE4 isoforms is fundamental to the compartmentalization of cAMP signaling pathways and is largely achieved via proteinprotein interactions. Increased knowledge of these protein-protein interactions and their regulatory properties could aid in the design of novel isoform-specific inhibitors with improved efficacy and fewer prohibitive side effects.
McCahill
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AC
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G128QQ, UK.
Huston
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E
Li
X
X
Houslay
M D
MD
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011487:Protein Conformation; D015398:Signal Transduction
D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4