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Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A
Open accessAbstract
We report here the cloning, expression, and characterization of a dual-substrate, cAMP and cGMP, cyclic nucleotide phosphodiesterase (PDE) from mouse. This PDE contains the consensus sequence for a PDE catalytic domain, but shares <50% sequence identity with the catalytic domains of all other known PDEs and, therefore, represents a new PDE gene family, designated PDE10A. The cDNA for PDE10A is 3,370 nt in length. It includes a full ORF, contains three in-frame stop codons upstream of the first methionine, and is predicted to encode a 779-aa enzyme. At the N terminus PDE10A has two GAF domains homologous to many signaling molecules, including PDE2, PDE5, and PDE6, which likely constitute a low-affinity binding site for cGMP. PDE10A hydrolyzes cAMP with a K m of 0.05 μM and cGMP with a K m of 3 μM. Although PDE10A has a lower K m for cAMP, the V max ratio (cGMP/cAMP) is 4.7. RNA distribution studies indicate that PDE10A is expressed at highest levels in testis and brain.
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Cites
Nakai, K., & Horton, P. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01336-x · Cited by 2,181
Cited by
Lugnier, C. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.07.003 · Cited by 870
Cyclic nucleotide phosphodiesterases
Essayan, D. M. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.119555 · Cited by 503
Phosphodiesterases in the CNS: targets for drug development
Menniti, F. S., Faraci, W. S., & Schmidt, C. J. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2058 · Cited by 391
Physiological Substrates of cAMP-Dependent Protein Kinase
Shabb, J. B. (2001) · Chemical Reviews · doi:10.1021/cr000236l · Cited by 373
Immunohistochemical Localization of Phosphodiesterase 2A in Multiple Mammalian Species
Stephenson, D. T., Coskran, T. M., Wilhelms, M. B., Adamowicz, W. O., O'Donnell, M. M., Muravnick, K. B., Menniti, F. S., Kleiman, R. J., & Morton, D. (2009) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.2009.953471 · Cited by 289
Metadata
- Authors
- Soderling, S. H., Bayuga, S. J., & Beavo, J. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-06-08
- Volume
- 96
- Issue
- 12
- Pages
- 7071-7076
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1975769625
- Cited by
- 374
- References
- 1
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- green
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- Soderling, S. H., Bayuga, S. J., & Beavo, J. A. (1999). Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.12.7071
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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