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The PDE4 cyclic AMP-specific phosphodiesterase family comprises a large number of different isoforms encoded by four distinct genes, with additional complexity arising through alternate mRNA splicing. This generates a number of distinct PDE4 isoforms with unique N-terminal regions. The range of such splice variants emanating from the four PDE4 genes appears to be highly conserved across species. One...
The calmodulin-stimulated cyclic nucleotide phosphodiesterases (PDE1s) constitute a large gene family and are found in a wide variety of tissues and cells. Because of the functional diversity of PDE1 genes and the observation that these isozymes often make up a major component of the total cyclic nucleotide hydrolytic activity in certain cell types, PDE1s are of growing interest as targets for therapeutic...
Three methods have been used to assess the conformational effects associated with ligand binding to two unrelated cyclic nucleotide receptor proteins: the cGMP-binding, cGMP-specific phosphodiesterase (cGB-PDE or PDE5A) and the cGMP-dependent protein kinase (PKG). The methods should be applicable to other proteins and to other types of modification such as phosphorylation. The procedures use either...
The photoreceptor phosphodiesterase (PDE6) is the central effector enzyme in the phototransduction cascade of photoreceptor cells. It is the only known PDE isoform the activity of which is regulated by interaction with a heterotrimeric G protein. The rod PDE6 holoenzyme is a tetrameric protein consisting of two large catalytic α and β subunits and two small γ subunits, which serve as potent inhibitors...
Facile manipulation and rapid regeneration have helped to establish the yeastSaccharomyces cerevisiaeas a genetic workhorse. More recently, these simple eukaryotes have been used for the biochemical analysis of mammalian proteins. This article describes the use of a yeast expression system for bothin vitroandin vivoassays of mammalian phosphodiesterase (PDE) activity using yeast cells devoid of endogenous...
With the cloning of cDNAs coding for the different phosphodiesterase 4 (PDE4) isoenzymes present in mammals, homogeneous preparations of these forms have become readily available. This strategy has greatly facilitated the understanding of the properties of the myriad of isoforms derived from the four PDE4 genes found in mammals, and has opened a new avenue to develop inhibitors with a different degree...
Cyclic nucleotide phosphodiesterases (PDEs) are represented by a superfamily of structurally and functionally related enzymes of which more than 30 different forms have so far been identified and grouped into seven broad gene families, some of which contain multiple genes and many splice variants, within a given gene family. Since all of the forms of PDE have the potential to regulate levels of the...
Phosphodiesterases (PDEs) include a large group of structurally related enzymes that belong to at least seven related gene families (PDEs 1–7) that differ in their primary structure, affinity for cAMP and cGMP, response to specific effectors, sensitivity to specific inhibitors, and regulatory mechanism. One characteristic of PDE3s involves their phosphorylation and activation in response to insulin...
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