Abstract
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.
Keywords: Cell signaling, PKA, cAMP, multi-targeting, disease, pharmacological treatment, intracellular signaling pathway components, spatiotemporal regulation, asthma, chronic obstructive pulmonary disease, COPD, cAMP pathway
Current Topics in Medicinal Chemistry
Title: The cAMP-Dependent Protein Kinase Pathway as Therapeutic Target – Possibilities and Pitfalls
Volume: 11 Issue: 11
Author(s): Rune Kleppe, Camilla Krakstad, Frode Selheim, Reidun Kopperud and Stein Ove Doskeland
Affiliation:
Keywords: Cell signaling, PKA, cAMP, multi-targeting, disease, pharmacological treatment, intracellular signaling pathway components, spatiotemporal regulation, asthma, chronic obstructive pulmonary disease, COPD, cAMP pathway
Abstract: 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.
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Cite this article as:
Kleppe Rune, Krakstad Camilla, Selheim Frode, Kopperud Reidun and Ove Doskeland Stein, The cAMP-Dependent Protein Kinase Pathway as Therapeutic Target – Possibilities and Pitfalls, Current Topics in Medicinal Chemistry 2011; 11 (11) . https://dx.doi.org/10.2174/156802611795589629
DOI https://dx.doi.org/10.2174/156802611795589629 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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