Alternative titles; symbols
HGNC Approved Gene Symbol: PDE1B
Cytogenetic location: 12q13.2 Genomic coordinates (GRCh38): 12:54,549,601-54,579,239 (from NCBI)
Cyclic nucleotide phosphodiesterases (PDEs) catalyze hydrolysis of the cyclic nucleotides cAMP and cGMP to the corresponding nucleoside 5-prime-monophosphates. Mammalian PDEs have been classified into several families based on their biochemical properties. Members of the PDE1 family, such as PDE1B, are calmodulin (see 114180)-dependent PDEs (CaM-PDEs) that are stimulated by a calcium-calmodulin complex (Repaske et al., 1992).
Using a PCR strategy, Repaske et al. (1992) cloned partial mouse and human cDNAs encoding a 63-kD CaM-PDE.
Jiang et al. (1996) reported the sequence of the complete coding region of human PDE1B1. The predicted 536-amino acid protein shares 96% amino acid identity with bovine, rat, and mouse PDE1B1.
Yu et al. (1997) expressed PDE1B1 in S. cerevisiae and found that it migrated as a 61-kD protein by Western blot analysis. Northern blot analysis revealed that PDE1B1 was expressed as multiple transcripts in a tissue-specific pattern. The highest mRNA levels were detected in brain, heart, and skeletal muscle. Using in situ hybridization, Yu et al. (1997) determined that PDE1B1 was expressed predominantly in neuronal cells of the cerebellum, hippocampus, and caudate.
Reed et al. (1998) cloned and characterized the mouse Pde1b gene, which encodes the 63-kD calcium/calmodulin-dependent PDE. They noted that this PDE isozyme is expressed in the central nervous system in the olfactory tract, dentate gyrus, and striatum, suggesting that it may participate in learning, memory, and regulation of phosphorylation of DARPP-32 in dopaminergic neurons.
Fidock et al. (2002) isolated a splice variant of PDE1B that they called PDE1B2. The deduced 516-amino acid protein differs from the 536-amino acid PDE1B1 protein only at its N terminus. Northern blot analysis detected PDE1B1 expression in several specific brain regions, particularly caudate nucleus and putamen, but not in spinal cord or any peripheral tissues. In contrast, PDE1B2 was highly expressed in spinal cord, with lower expression in thyroid, thymus, uterus, small intestine, putamen, and caudate nucleus. Expression of PDE1B2 was not detected in other tissues.
Using RT-PCR, Jiang et al. (1996) found that PDE1B1 was expressed in several lymphoblastoid and leukemic cell lines, but not in normal, resting peripheral blood lymphocytes (PBLs). However, PDE1B1 expression was induced in PBLs following mitogenic stimulation. Inhibition of PDE1B1 expression in the lymphoblastic and leukemic cell lines caused the cells to undergo apoptosis, suggesting a novel therapeutic strategy for the treatment of leukemia.
Yu et al. (1997) found that recombinant PDE1B1 protein had biochemical properties consistent with those of a CaM-PDE.
By analysis of somatic cell hybrids and by inclusion in a mapped YAC, Yu et al. (1997) localized the PDE1B1 gene to chromosome 12q13. Using fluorescence in situ hybridization, Reed et al. (1998) localized the Pde1b gene to the distal tip of mouse chromosome 15.
Yu et al. (1997) isolated a partial PDE1B1 genomic sequence and found that 2 splice junctions within the region encoding the catalytic domain are conserved in rat Pde4b (600127) and Pde4d (600129) and in the Drosophila 'dunce' PDE, suggesting that the catalytic domains of PDEs are derived from a common ancestral gene.
Reed et al. (1998) found that the mouse Pde1b gene shares many similar or identical exon boundaries as well as considerable sequence identity with the rat Pde4b and Pde4d genes and the Drosophila 'dunce' cAMP-specific Pde gene dnc, suggesting that these genes all arose from a common ancestor.
Fidock, M., Miller, M., Lanfear, J. Isolation and differential tissue distribution of two human cDNAs encoding PDE1 splice variants. Cell. Signal. 14: 53-60, 2002. [PubMed: 11747989] [Full Text: https://doi.org/10.1016/s0898-6568(01)00207-8]
Jiang, X., Li, J., Paskind, M., Epstein, P. M. Inhibition of calmodulin-dependent phosphodiesterase induces apoptosis in human leukemic cells. Proc. Nat. Acad. Sci. 93: 11236-11241, 1996. [PubMed: 8855339] [Full Text: https://doi.org/10.1073/pnas.93.20.11236]
Reed, T. M., Browning, J. E., Blough, R. I., Vorhees, C. V., Repaske, D. R. Genomic structure and chromosome location of the murine PDE1B phosphodiesterase gene. Mammalian Genome 9: 571-576, 1998. [PubMed: 9657856] [Full Text: https://doi.org/10.1007/s003359900820]
Repaske, D. R., Swinnen, J. V., Jin, S.-L. C., Van Wyk, J. J., Conti, M. A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs: molecular cloning of the cDNA encoding the 63-kDa calmodulin-dependent phosphodiesterase. J. Biol. Chem. 267: 18683-18688, 1992. [PubMed: 1326532]
Yu, J., Wolda, S. L., Frazier, A. L. B., Florio, V. A., Martins, T. J., Snyder, P. B., Harris, E. A. S., McCaw, K. N., Farrell, C. A., Steiner, B., Bentley, J. K., Beavo, J. A., Ferguson, K., Gelinas, R. Identification and characterisation of a human calmodulin-stimulated phosphodiesterase PDE1B1. Cell. Signal. 9: 519-529, 1997. [PubMed: 9419816] [Full Text: https://doi.org/10.1016/s0898-6568(97)00046-6]