RRC ID |
29048
|
著者 |
Bosgraaf L, Russcher H, Snippe H, Bader S, Wind J, Van Haastert PJ.
|
タイトル |
Identification and characterization of two unusual cGMP-stimulated phoshodiesterases in dictyostelium.
|
ジャーナル |
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.
|
巻・号 |
13(11)
|
ページ |
3878-89
|
公開日 |
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
|
引用数 |
35
|
WOS 分野
|
CELL BIOLOGY
|
リソース情報 |
細胞性粘菌 |
S00142
S00339
S00340 |