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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
3',5'-cyclic nucleotide phosphodiesterase 11A: localization in human tissues
K Loughney1, J Taylor, V A Florio
1Icos Corporation, Bothell, WA, USA. kloughney@icos.com
Insights
The study found that only one variant, PDE11A4, of the 3
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- 3',5'-Cyclic nucleotide phosphodiesterase 11 (PDE11) is a recently identified PDE family with one gene, PDE11A, and four splice variants.
- The physiological function of PDE11A remains largely unknown.
- Tadalafil, a PDE5A inhibitor, shows partial inhibition of PDE11, suggesting potential interactions.
Purpose of the Study:
- To investigate the tissue expression pattern of PDE11A protein in humans.
- To determine which PDE11A splice variants are expressed at the protein level.
Main Methods:
- Analysis of PDE11A mRNA transcripts.
- Detection of PDE11A protein using immunohistochemistry in various human tissues.
- Antibody staining to identify PDE11A protein localization.
Main Results:
- Only the PDE11A4 splice variant protein was detected in human prostate, pituitary, heart, and liver.
- Strong PDE11A4 staining was observed in prostate glandular epithelium and weak staining in cardiac parasympathetic ganglia.
- No PDE11A protein was detected in human blood vessels, cardiac myocytes, skeletal muscle, testis, or penis.
Conclusions:
- PDE11A4 is the predominant or sole expressed protein variant of PDE11A in key human tissues.
- The tissue-specific expression of PDE11A4 suggests a targeted physiological role.
- Further research is needed to elucidate the specific functions of PDE11A4 in the prostate, pituitary, heart, and liver.
Abstract:
3',5'-Cyclic nucleotide phosphodiesterase 11 (PDE11) is the most recently discovered family of human 3',5'-cyclic nucleotide phosphodiesterases (PDEs). This family contains one gene, PDE11A, with four splice variants (PDE11A1-PDE11A4). The physiological role of PDE11A has not been determined. Tadalafil (Cialis), a PDE5A inhibitor used for the treatment of male erectile dysfunction, has been reported to partially inhibit PDE11. It was therefore of interest to consider the pattern of expression of PDE11 in human tissues. Although four PDE11A mRNA transcripts have been reported, we detected protein corresponding to only one of them, PDE11A4, in human prostate, pituitary, heart and liver. Using immunohistochemistry, there was strong PDE11A antibody staining in the glandular epithelium of the prostate and weak staining of neuronal cells within parasympathetic ganglia in the heart. No PDE11A protein was detected in blood vessels or cardiac myocytes. None of the four potential PDE11A proteins were detected in human skeletal muscle, testis, or penis.
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