Disease relevance of PDE4C

• Our data suggest that PDE4C may play an important role in the airway inflammation, remodeling and goblet cell hyperplasia after repeated challenge of sensitized rats [1].
• The PDE4C-delta54 variant was found only in testis and the 5'-extended region of PDE4C-791 was seen only in lung and the melanoma cell line G361 [2].

High impact information on PDE4C

• We have isolated cDNAs for four human genes (DPDE1 through DPDE4) closely related to the dnc learning and memory locus of Drosophila melanogaster [3].
• Gene expression for PDE4D and PDE4C was significantly up-regulated during in vitro decidualization [4].
• Diphosphodiester resonances (DPDE, mainly UDP-N-acetyl-glucosamine and UDP-N-acetylgalactosamine) were not detected in the in vivo spectrum and were only apparent in the spectrum of the perchloric acid extract of the cells, indicating that these compounds have a restricted mobility in the intracellular compartment [5].
• Finally, PDE4D5 and PDE4C were differentially regulated in lung macrophages when compared with monocytes of the same subjects, irrespective of the disease state [6].
• PDE4C was detected in all cells analyzed except for T cells [6].

Biological context of PDE4C

• Analysis of this locus indicated that the PDE4C gene spans at least 38 kb, consists of at least 18 exons, and contains the marker D19S212 within an intron [7].
• Overlapping cosmid clones spanning the human PDE4C gene were identified and characterised [7].
• Fluorescent in situ hybridisation localised PDE4C to the p13.1 region of human chromosome 19 [7].
• The longest open reading frame (ORF) of 791 amino acids (aa) is encoded by PDE4C-791, which is similar to a recently described cDNA [Engels, P., Sullivan, M., Muller, T. and Lubbert, H. FEBS Lett. 358 (1995) 305-10], except that an alternative 5'-end sequence upstream of the first methionine extends the PDE4C-791 ORF by 79 aa [2].

Anatomical context of PDE4C

• In contrast, PDE4C in human brain, presents a more restricted distribution, limited to cortex, some thalamic nuclei and cerebellum [8].
• Multiple splice variants of phosphodiesterase PDE4C cloned from human lung and testis [2].
• The PDE4C2 cDNA was transfected into both COS 1 cells and yeast cells, and shown to direct the expression of an 80 kD polypeptide by Western blotting using a PDE4C specific antiserum [9].
• Finally, Th1 cells showed reduced gene expression for the PDE4C isoform and a lack of gene expression for the PDE4D isoform by reverse transcription-polymerase chain reaction, compared to the Th2 cells [10].
• PDE4C was not detected in either the medulla or nodose ganglion [11].

Associations of PDE4C with chemical compounds

• PDE4C is one of four mammalian genes that encode multiple PDE4 cyclic AMP-specific phosphodiesterase isoforms that are inhibited by rolipram [7].
• The predicted 426 aa protein initiates at a methionine 365 aa within PDE4C-791 [2].
• To elucidate further the possible biochemical mechanisms associated with these alterations, we analyzed the phosphorous metabolites by MR spectroscopy and found that the major metabolites were PME, (PC, PE) and DPDE (UDP-GalNAc, UDP-GLcNAc) [12].

Other interactions of PDE4C

• PDE4A and PDE4B mRNAs also are markedly abundant, whereas lower expression is observed for PDE4C mRNAs [13].

References