Download PDF
Horm Metab Res 2012; 44(10): 776-785
DOI: 10.1055/s-0032-1312646
Review
© Georg Thieme Verlag KG Stuttgart · New York

Cyclic Nucleotide Phosphodiesterase 3 Signaling Complexes

F. Ahmad
1   Cardiovascular Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA
,
E. Degerman
2   Department of Experimental Medical Science, Division for Diabetes, Metabolism and Endocrinology, Lund University, Lund, Sweden
,
V. C. Manganiello
1   Cardiovascular Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA
› Author Affiliations
Further Information

Publication History

received 06 January 2012

accepted 19 April 2012

Publication Date:
12 June 2012 (online)

Also available at
   Buy Article Permissions and Reprints

Corrected by:

Cyclic Nucleotide Phosphodiesterase 3 Signaling ComplexesHorm Metab Res 2012; 44(12): 930-930
DOI: 10.1055/s-0032-1327600

Abstract

The superfamily of cyclic nucleotide phosphodiesterases is comprised of 11 gene families. By hydrolyzing cAMP and cGMP, PDEs are major determinants in the regulation of intracellular concentrations of cyclic nucleotides and cyclic nucleotide-dependent signaling pathways. Two PDE3 subfamilies, PDE3A and PDE3B, have been described. PDE3A and PDE3B hydrolyze cAMP and cGMP with high affinity in a mutually competitive manner and are regulators of a number of important cAMP- and cGMP-mediated processes. PDE3B is relatively more highly expressed in cells of importance for the regulation of energy homeostasis, including adipocytes, hepatocytes, and pancreatic β-cells, whereas PDE3A is more highly expressed in heart, platelets, vascular smooth muscle cells, and oocytes. Major advances have been made in understanding the different physiological impacts and biochemical basis for recruitment and subcellular localizations of different PDEs and PDE-containing macromolecular signaling complexes or signalosomes. In these discrete compartments, PDEs control cyclic nucleotide levels and regulate specific physiological processes as components of individual signalosomes which are tethered at specific locations and which contain PDEs together with cyclic nucleotide-dependent protein kinases (PKA and PKG), adenylyl cyclases, Epacs (guanine nucleotide exchange proteins activated by cAMP), phosphoprotein phosphatases, A-Kinase anchoring proteins (AKAPs), and pathway-specific regulators and effectors. This article highlights the identification of different PDE3A- and PDE3B-containing signalosomes in specialized subcellular compartments, which can increase the specificity and efficiency of intracellular signaling and be involved in the regulation of different cAMP-mediated metabolic processes.

Key words

phosphodiesterase - protein kinase A - signalosomes