Studies described in the present review highlight the importance of this relationship for individual cardiac PKA substrates and we provide an overview of how this signalling paradigm is coordinated to promote efficient adrenergic enhancement of cardiac function.

PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization. cAMP is a second messenger that controls many key cellular functions. The only way to inactivate cAMP is to degrade it through the action of cAMP phosphodiesterases (PDEs).

Nov 30, 2014 · PDE4 family cAMP phosphodiesterases play a pivotal role in determining compartmentalised cAMP signalling through targeted cAMP breakdown. Expressing the widely found PDE4D5 isoform, as both bait and prey in a yeast 2-hybrid system, we demonstrated interaction consistent with the notion that long PDE4 isoforms form dimers.

Inhibition of PDE4 is predicted to have diverse effects via the elevation of the level of cyclic adenosine monophosphate (cAMP) and the subsequent regulation of a wide array of genes and proteins. It has been identified that PDE4 is a promising therapeutic target for the treatment of diverse pulmonary, dermatological, and severe neurological ...

Jan 31, 2018 · The ability of cAMP to elicit cell surface receptor-specific responses relies on its compartmentalisation by cAMP hydrolysing enzymes known as phosphodiesterases. One family of these enzymes, PDE4, is particularly important in the cardiovascular system, where it has been extensively studied and shown to orchestrate complex, localised signalling ...

Dec 19, 2024 · PDE4 plays a central role in modulating inflammatory responses by regulating cAMP levels in immune cells, including T lymphocytes, macrophages, and dendritic cells. Elevated PDE4 activity leads to reduced intracellular cAMP levels, which enhances the production of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β [ 19 ].

The phosphodiesterase 4 (PDE4) enzyme family plays a pivotal role in regulating levels of the second messenger cAMP. Consequently, PDE4 inhibitors have been investigated as a therapeutic strategy to enhance cAMP signaling in a broad range of diseases, including several types of cancers, as well as in various neurologic, dermatological, and ...

The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the secondary messenger, cAMP , which is a regulator and mediator of a number of cellular responses to extracellular signals.

Feb 25, 2025 · Spatial transcriptome sequencing and targeted Pde4b protein knockdown show that acute stress reduces Pde4b-regulated cAMP signaling in AUD GABA -S1Tr Sst projections, leading to decreased S1Tr Sst neuron activity in subsequent behavioral tests.

The PDE4 cyclic nucleotide phosphodiesterases are essential regulators of cAMP abundance in the CNS through their ability to regulate PKA activity, the phosphorylation of CREB, and other important elements of signal transduction.