| Autor: |
Bosgraaf, Leonard, Russcher, Henk, Snippe, Helena, Bader, Sonya, Wind, Joyce, Van Haastert, Peter J.M. |
| Zdroj: |
Molecular Biology of the Cell; November 2002, Vol. 13 Issue: 11 p3878-3889, 12p |
| Abstrakt: |
Recently, we recognized two genes, gbpAandgbpB, encoding putative cGMP-binding proteins with a Zn2+-hydrolase domain and two cyclic nucleotide binding domains. The Zn2+-hydrolase domains belong to the superfamily of β-lactamases, also harboring a small family of class II phosphodiesterases from bacteria and lower eukaryotes. Gene inactivation and overexpression studies demonstrate thatgbpAencodes 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 gbpBgene is expressed mainly in the multicellular stage and seems to encode a dual specificity phosphodiesterase with preference for cAMP. The enzyme hydrolyses cAMP ∼9-fold faster than cGMP and is activated by cAMP and cGMP with aKAvalue of ∼0.7 and 2.3 μM, respectively. Cells with a deletion of the gbpBgene have increased basal and receptor stimulated cAMP levels and are sporogeneous. We propose that GbpA and GbpB hydrolyze the substrate in the Zn2+-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. |
| Databáze: |
Supplemental Index |
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