Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sensing of an odorant by an animal must be a rapid but transient process, requiring an instant response and also a speedy termination of the signal. Previous biochemical and electrophysiological studies suggest that one or more phosphodiesterases (PDEs) may play an essential role in the rapid termination of the odorant-induced cAMP signal. Here we report the molecular cloning, expression, and characterization of a cDNA from rat olfactory epithelium that encodes a member of the calmodulin-dependent PDE family designated as PDE1C. This enzyme shows high affinity for cAMP and cGMP, having a Km for cAMP much lower than that of any other neuronal Ca2+/calmodulin-dependent PDE. The mRNA encoding this enzyme is highly enriched in olfactory epithelium and is not detected in six other tissues tested. However, RNase protection analyses indicate that other alternative splice variants related to this enzyme are expressed in several other tissues. Within the olfactory epithelium, this enzyme appears to be expressed exclusively in the sensory neurons. The high affinity for cAMP of this Ca2+/calmodulin-dependent PDE and the fact that its mRNA is highly concentrated in olfactory sensory neurons suggest an important role for it in a Ca(2+)-regulated olfactory signal termination.
 ...
PMID:Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons. 756 96

cDNAs corresponding to two human calcium, calmodulin (CaM)-regulated 3',5'-cyclic nucleotide phosphodiesterases (PDEs) were isolated. One, Hcam1 (PDE1A3), corresponds to the bovine 61-kDa CaM PDE (PDE1A2). The second, Hcam3 (PDE1C), represents a novel phosphodiesterase gene. Hcam1 encodes a 535-amino acid protein that differs most notably from the bovine 61-kDa CaM PDE by the presence of a 14-amino acid insertion and a divergent carboxyl terminus. RNase protection studies indicated that Hcam1 is represented in human RNA from several tissues, including brain, kidney, testes, and heart. Two carboxyl-terminal splice variants for Hcam3 were isolated. One, Hcam3b (PDE1C1), encodes a protein 634 amino acids (72 kDa) in length. The other, Hcam3a (PDE1C3), diverges from Hcam3b 4 amino acids from the carboxyl terminus of Hcam3b, and extends an additional 79 amino acids. All the cDNAs isolated for Hcam3a are incomplete; they do not include the 5'-end of the open reading frame. Northern analysis revealed that both splice variants were expressed in several tissues, including brain and heart, and that there may be additional splice variants. Amino-truncated recombinant proteins were expressed in yeast and characterized biochemically. Hcam3a has a high affinity for both cAMP and cGMP and thus has distinctly different kinetic parameters from Hcam1, which has a higher affinity for cGMP than for cAMP. Both PDE1C enzymes were inhibited by isobutylmethylxanthine, 8-methoxymethyl isobutylmethylxanthine, zaprinast, and vinpocetine.
 ...
PMID:Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated, 3',5'-cyclic nucleotide phosphodiesterases. 855 89

We report here the identification of cDNAs for three new mouse PDE1C splice variants and the characterization of their kinetics, regulation by Ca2+, sensitivities to inhibitors, and tissue/cellular expression patterns. Sequence analysis indicated that these three cDNAs (PDE1C1, PDE1C4, and PDE1C5), together with our previously reported PDE1C2 and PDE1C3, are alternative splice products of the PDE1C gene. The results from RNase protection analysis and in situ hybridization indicated that the expression of the different PDE1C splice variants is differentially regulated in a tissue/cell-specific manner. Particularly, high levels of PDE1C mRNAs were found in the olfactory epithelium, testis, and several regions of mouse brain such as cerebellar granule cells. All of these splice variants have similar kinetic properties, showing high affinities and approximately the same relative Vmax values for both cAMP and cGMP. However, they responded to Ca2+ stimulation differently. In addition, they show different sensitivities to the calmodulin-dependent phosphodiesterase inhibitors, KS505a and SCH51866. Substrate competition experiments suggested the presence of only one catalytic site on these PDE1C isozymes for both cAMP and cGMP. In summary, these findings suggest that the PDE1C gene undergoes tissue-specific alternative splicing that generates structurally and functionally diverse gene products.
 ...
PMID:The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner. 881 Mar 48