Cloning and characterization of novel PDE4D isoforms PDE4D6 and PDE4D7

Autor: Christopher J. Leonard, Caryn Gunwaldsen, Bozena Bugaj-Gaweda, Xiaonan Xin, Michael De Vivo, Chengjun Deng, Daguang Wang, Axel Unterbeck, Yinghe Hu, May Kwan
Rok vydání: 2003
Předmět:
Gene isoform
Male
Blotting
Western
Molecular Sequence Data
Biology
Spodoptera
CREB
Transfection
Binding
Competitive
Polymerase Chain Reaction
Gene Expression Regulation
Enzymologic
Cell Line
Mice
Catalytic Domain
Cyclic AMP
Animals
Humans
Amino Acid Sequence
Binding site
Cloning
Molecular
Phosphorylation
Cyclic AMP Response Element-Binding Protein
Promoter Regions
Genetic
Gene
Protein kinase C
Conserved Sequence
Cloning
Binding Sites
Base Sequence
Dose-Response Relationship
Drug
Sequence Homology
Amino Acid
Kinase
Cell Biology
Sequence Analysis
DNA
Cyclic AMP-Dependent Protein Kinases
Cyclic Nucleotide Phosphodiesterases
Type 3
Cyclic Nucleotide Phosphodiesterases
Type 4
Rats
Isoenzymes
Alternative Splicing
Kinetics
Biochemistry
3'
5'-Cyclic-AMP Phosphodiesterases
biology.protein
Rolipram
Sequence Alignment
Zdroj: Cellular signalling. 15(9)
ISSN: 0898-6568
Popis: We report here the cloning and characterization of two novel PDE4D isoforms, PDE4D6 and PDE4D7. PDE4D6 is a supershort form and PDE4D7 a long form of PDE4D. In addition, we have identified another novel long-form variant, PDE4D8, in silico. Like other isoforms, PDE4D6 and PDE4D7 are differentially expressed. Expression of PDE4D6 is restricted to brain whereas PDE4D7 is widely expressed in many tissues. Baculovirus-expressed recombinant PDE4D6 and PDE4D7 enzymes have high affinity for cyclic AMP (cAMP) and are inhibited by rolipram. The activity of PDE4D7, not PDE4D6, is elevated by a protein kinase A (PKA)-dependent mechanism, presumably through phosphorylation of the conserved PKA site in the upstream conserved region 1 (UCR1) domain. In agreement with early reports, human PDE4D6 and PDE4D7 are localized on genomic fragments of chromosome 5. Examination of the promoter regions reveals multiple CREB binding sites upstream of the starting methionine (Met) of each gene, suggesting that the cAMP/PKA signaling pathway may regulate transcriptional expression of PDE4D6 and PDE4D7.
Databáze: OpenAIRE
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