The cAMP-dependent protein kinase pathway as therapeutic target: possibilities and pitfalls

• Published in: Current topics in medicinal chemistry Vol. 11; no. 11; p. 1393
• Main Authors: Kleppe, Rune, Krakstad, Camilla, Selheim, Frode, Kopperud, Reidun, Døskeland, Stein Ove
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.06.2011
• Subjects: Animals; Cyclic AMP - antagonists & inhibitors; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - metabolism; Humans; Models, Biological; Protein Kinase Inhibitors - pharmacology; Signal Transduction - drug effects; Structure-Activity Relationship
• ISSN: 1873-4294
• DOI: 10.2174/156802611795589629

The prototype second messenger cAMP and its major mediator, the cAMP-dependent protein kinase (PKA), is able to control simultaneously multiple processes within the same cell. This appears to be achieved through its unique dissociative regulation and the spatiotemporal regulation of both cAMP and PKA. The widespread tissue distribution and physiological function of this pathway makes it an attractive, but challenging pharmacological target. We will discuss current progress in manipulating the fine-tuning of PKA, and outline so far underexploited possibilities for therapy, such as novel ways to target specific substrates and catalytic cycle intermediates of PKA. An attractive strategy to achieve a more focused pharmacological treatment is to combine more traditional targeting of extracellular receptors or ligands with that of intracellular signaling pathway components. The cAMP signaling pathway provides a variety of possibilities for such an approach.