RRC ID 29048
Author Bosgraaf L, Russcher H, Snippe H, Bader S, Wind J, Van Haastert PJ.
Title Identification and characterization of two unusual cGMP-stimulated phoshodiesterases in dictyostelium.
Journal Mol Biol Cell
Abstract Recently, we recognized two genes, gbpA and gbpB, encoding putative cGMP-binding proteins with a Zn(2+)-hydrolase domain and two cyclic nucleotide binding domains. The Zn(2+)-hydrolase domains belong to the superfamily of beta-lactamases, also harboring a small family of class II phosphodiesterases from bacteria and lower eukaryotes. Gene inactivation and overexpression studies demonstrate that gbpA encodes the cGMP-stimulated cGMP-phosphodiesterase that was characterized biochemically previously and was shown to be involved in chemotaxis. cAMP neither activates nor is a substrate of GbpA. The gbpB gene is expressed mainly in the multicellular stage and seems to encode a dual specificity phosphodiesterase with preference for cAMP. The enzyme hydrolyses cAMP approximately 9-fold faster than cGMP and is activated by cAMP and cGMP with a K(A) value of approximately 0.7 and 2.3 microM, respectively. Cells with a deletion of the gbpB gene have increased basal and receptor stimulated cAMP levels and are sporogeneous. We propose that GbpA and GbpB hydrolyze the substrate in the Zn(2+)-hydrolase domain, whereas the cyclic nucleotide binding domains mediate activation. The human cGMP-stimulated cAMP/cGMP phosphodiesterase has similar biochemical properties, but a completely different topology: hydrolysis takes place by a class I catalytic domain and GAF domains mediate cGMP activation.
Volume 13(11)
Pages 3878-89
Published 2002-11-1
DOI 10.1091/mbc.e02-05-0302
PMID 12429832
PMC PMC133600
MeSH 3',5'-Cyclic-GMP Phosphodiesterases / chemistry 3',5'-Cyclic-GMP Phosphodiesterases / genetics 3',5'-Cyclic-GMP Phosphodiesterases / metabolism* Amino Acid Sequence Animals Cyclic AMP / metabolism Cyclic GMP / metabolism Dictyostelium / cytology Dictyostelium / enzymology* Dictyostelium / genetics Dictyostelium / physiology Gene Targeting Humans Molecular Sequence Data Phenotype Protein Structure, Tertiary Sequence Alignment
IF 3.791
Times Cited 35
Cellular slime molds S00142 S00339 S00340