Alternative titles; symbols
HGNC Approved Gene Symbol: PDE3B
Cytogenetic location: 11p15.2 Genomic coordinates (GRCh38): 11:14,643,804-14,872,044 (from NCBI)
Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of related enzymes involved in many regulatory pathways. The PDE3 family is characterized by high affinity for cAMP, inhibition by cGMP, sensitivity to specific inhibitors such as cilostamide and milrinone, and by phosphorylation and activation in response to insulin and agents that increase cAMP. Miki et al. (1996) used a rat PDE3B cDNA to screen a human fat cDNA library. They assembled a complete PDE3B cDNA coding sequence by assembling partial cDNA clones, genomic clones, and PCR products. This coding sequence predicts a protein of 1,112 amino acids with 81% amino acid identity with rat PDE3B. Northern blot analysis showed low levels of PDE3B expression in liver, spleen, lung, and kidney, and abundant 5.4- and 6.4-kb transcripts in adipose tissue from several locations. Lobbert et al. (1996) also isolated cDNAs of human PDE3B and reported similar findings.
Using male Sprague-Dawley rats implanted with third intracerebroventricular cannulae, Zhao et al. (2002) found that cilostamide, a PDE3B inhibitor, reversed the established effects of leptin (164160) on food intake and body weight; blocked, at the hypothalamic level, the leptin-induced tyrosine phosphorylation of signal transducer and activator of transcription-3 (STAT3; 102582); and blocked the DNA binding of STAT3 protein. In addition, Zhao et al. (2002) showed that intracerebroventricular administration of leptin increased hypothalamic phosphatidylinositol 3-kinase (PI3K; see 601232) and PDE3B activities and decreased cAMP concentration. Zhao et al. (2002) concluded that a PI3K-PDE3B-cAMP pathway interacting with the JAK2 (147796)-STAT3 pathway constitutes a critical component of leptin signaling in the hypothalamus.
Regulatory CD4-positive T cells, or Tr cells, prevent self-destructive immune responses, and their development is critically dependent on FOXP3 (300292). Gavin et al. (2007) studied mouse T cells that actively transcribed a Foxp3-null allele, but lacked Foxp3 protein. Using flow cytometric and microarray analyses, they found that, although Foxp3 function was required for Tr suppressor cell activity, Foxp3 largely amplified and fixed preexisting molecular features of Tr cells. Furthermore, Foxp3 solidified Tr-cell lineage stability by modifying cell surface and signaling molecules, including Foxp3-dependent repression of Pde3b. Introduction of Pde3b into Tr cells and transfer of these cells to T-cell-deficient mice substantially reduced the number of Tr cells. Gavin et al. (2007) proposed that reduced PDE3B expression may be a unique marker of Tr cells.
Miki et al. (1996) isolated and analyzed genomic clones of human PDE3B. They found that the PDE3B gene was encoded on 16 exons spanning 114 kb.
Miki et al. (1996) used fluorescence in situ hybridization to localize the human PDE3B gene to chromosome 11p15. Lobbert et al. (1996) sublocalized this mapping to 11p15.1-p15.2 using a PCR mapping panel. They noted evidence suggesting that this chromosomal area harbors genes involved in obesity and noninsulin-dependent diabetes mellitus.
Miki et al. (1996) noted the existence of a G/A polymorphism in the coding region of the PDE3B gene and polymorphic dinucleotide repeats in 2 of the introns.
Choi et al. (2006) found that newborn Pde3b-knockout mice exhibited no obvious physical defects, and their growth, development, behavior, and fertility appeared normal. Pde3b-knockout mice were slightly heavier than controls, and they exhibited variations in coat color from white to yellowish brown. The weight of gonadal adipose tissue was lower in knockout than wildtype mice, and the mean cell diameter of knockout adipocytes was smaller than normal. Triglyceride content was significantly increased in livers of knockout mice and was associated with increased expression of fatty acid synthase (FASN; 600212). Pde3b-knockout mice exhibited multiple alterations in regulation of lipolysis, lipogenesis, and insulin secretion, as well as signs of peripheral insulin resistance.
This gene has been referred to as PDE3A. However, it has been assigned the symbol PDE3B by GDB/HUGO. The symbol PDE3A has been assigned to myocardial cGMP-inhibited cAMP phosphodiesterase (123805).
Choi, Y. H., Park, S., Hockman, S., Zmuda-Trzebiatowska, E., Svennelid, F., Haluzik, M., Gavrilova, O., Ahmad, F., Pepin, L., Napolitano, M., Taira, M., Sundler, F., Holst, L. S., Degerman, E., Manganiello, V. C. Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice. J. Clin. Invest. 116: 3240-3251, 2006. [PubMed: 17143332] [Full Text: https://doi.org/10.1172/JCI24867]
Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A., Rudensky, A. Y. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445: 771-775, 2007. [PubMed: 17220874] [Full Text: https://doi.org/10.1038/nature05543]
Lobbert, R. W., Winterpacht, A., Seipel, B., Zabel, B. U. Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A)--a gene involved in fat metabolism located at 11p15.1. Genomics 37: 211-218, 1996. [PubMed: 8921398] [Full Text: https://doi.org/10.1006/geno.1996.0544]
Miki, T., Taira, M., Hockman, S., Shimada, F., Lieman, J., Napolitano, M., Ward, D., Taira, M., Makino, H., Manganiello, V. C. Characterization of the cDNA and gene encoding human PDE3B, the cGIP1 isoform of the human cyclic GMP-inhibited cyclic nucleotide phosphodiesterase family. Genomics 36: 476-485, 1996. [PubMed: 8884271] [Full Text: https://doi.org/10.1006/geno.1996.0493]
Zhao, A. Z., Huan, J.-N., Gupta, S., Pal, R., Sahu, A. A phosphatidylinositol 3-kinase-phosphodiesterase 3B-cyclic AMP pathway in hypothalamic action of leptin on feeding. Nature Neurosci. 5: 727-728, 2002. [PubMed: 12101402] [Full Text: https://doi.org/10.1038/nn885]