The biology of cyclic nucleotide phosphodiesterases.

Cyclic nucleotide phosphodiesterases: relating structure and function.

Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of metallophosphohydrolases that specifically cleave the 3',5'-cyclic phosphate moiety of cAMP and/or cGMP to produce the corresponding 5'-nucleotide. PDEs are critical determinants for modulation of cellular levels of cAMP and/or cGMP by many stimuli. Eleven families of PDEs with varying selectivities for cAMP or cGMP have been...

Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling.

Cyclic nucleotide phosphodiesterases as targets for treatment of haematological malignancies.

The cAMP signalling pathway has emerged as a key regulator of haematopoietic cell proliferation, differentiation and apoptosis. In parallel, general understanding of the biology of cyclic nucleotide PDEs (phosphodiesterases) has advanced considerably, revealing the remarkable complexity of this enzyme system that regulates the amplitude, kinetics and location of intracellular cAMP-mediated sign...

A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs.

We have isolated cDNAs for four human genes (DPDE1 through DPDE4) closely related to the dnc learning and memory locus of Drosophila melanogaster. The deduced amino acid sequences of the Drosophila and human proteins have considerable homology, extending beyond the putative catalytic region to include two novel, highly conserved, upstream conserved regions (UCR1 and UCR2). The upstream conserve...

Functions of PDE3 Isoforms in Cardiac Muscle

Isoforms in the PDE3 family of cyclic nucleotide phosphodiesterases have important roles in cyclic nucleotide-mediated signalling in cardiac myocytes. These enzymes are targeted by inhibitors used to increase contractility in patients with heart failure, with a combination of beneficial and adverse effects on clinical outcomes. This review covers relevant aspects of the molecular biology of the...

Zinc-Mediated Inhibition of Cyclic Nucleotide Phosphodiesterase Activity and Expression Suppresses TNF- and IL-1 Production in Monocytes by Elevation of Guanosine 3 ,5 -Cyclic Monophosphate