Identification and Characterisation of a Human Calmodulin-Stimulated Phosphodiesterase PDE1B1

Autor: B. Steiner, K. N. Mccaw, J. K. Bentley, C. A. Farrell, J. Yu, Joseph A. Beavo, R. Gelinas, Edith A. S. Harris, Ken Ferguson, A. L. B. Frazier, Peter B. Snyder, Timothy J. Martins, Sharon L. Wolda, Vincent A. Florio
Rok vydání: 1997
Předmět:
Zdroj: Cellular Signalling. 9:519-529
ISSN: 0898-6568
DOI: 10.1016/s0898-6568(97)00046-6
Popis: A cDNA encoding a calmodulin-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE) was isolated from a human brain cDNA library. The cDNA, designated HSPDE1B1, encoded a protein of 536 amino acids that shared 96% sequence identity with the bovine "63 kDa" calmodulin-stimulated PDE. The recombinant protein had cyclic nucleotide phosphodiesterase activity that was stimulated approximately 2-fold by Ca2+/calmodulin and preferred cGMP as substrate. In addition, the enzymatic activity of HSPDE1B1 was inhibited by phosphodiesterase inhibitors with potencies similar to that displayed toward the bovine PDE1 enzymes: IBMX approximately equal to 8-methoxymethyl-IBMXvinpocetine approximately equal to zaprinastcilostamiderolipram. HSPDE1B1 mRNA was found predominantly in the brain. Lower mRNA levels were found in heart and skeletal muscle. In situ hybridisation of brain revealed expression of HSPDE1B1 predominately in neuronal cells of the cerebellum, hippocampus and caudate. The HSPDE1B1 gene was mapped to human chromosome 12. A partial genomic sequence of HSPDE1B1 was isolated and shown to contain two splice junctions that are conserved in the rat PDE4 and the Drosophila dunce genes.
Databáze: OpenAIRE