Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
Disease
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Enzyme
Compound
Query: EC:4.6.1.1 (
adenylate cyclase
)
19,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
ARPP-21
(cAMP-regulated phosphoprotein, Mr = 21,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate), a phosphoprotein substrate for cAMP-dependent protein kinase, is unevenly distributed in adult rat brain. Using immunoblotting and phosphorylation in vitro followed by immunoprecipitation,
ARPP-21
was found to be enriched in caudate-putamen, substantia nigra, nucleus accumbens and olfactory tubercle. Intermediate levels were found in cerebral cortex and hippocampus.
ARPP-21
was very low in most other brain areas and was not detected in any of the peripheral tissues studied. Following unilateral lesion of the caudate-putamen with quinolinic acid, a marked decrease in the levels of
ARPP-21
was observed in both the lesioned caudate-putamen (-75%) and the ipsilateral substantia nigra (-70%) compared with the unlesioned side. This result demonstrates the enrichment of
ARPP-21
in striatonigral neurons. In slices of caudate-putamen, substantia nigra or cerebral cortex incubated in vitro, the phosphorylation of
ARPP-21
was enhanced by 8-Br-cAMP, a stable analog of cAMP. In striatal slices, forskolin, a compound which stimulates
adenylate cyclase
directly, enhanced the phosphorylation of
ARPP-21
with an EC50 of 0.5 microM. In conclusion,
ARPP-21
is a neuron-specific phosphoprotein enriched in specific brain areas which are known to receive a rich dopaminergic innervation and to contain high levels of D1 dopamine receptors. The phosphorylation of
ARPP-21
is likely to mediate some of the intracellular effects of neurotransmitters which stimulate
adenylate cyclase
in these regions, in particular dopamine and vasoactive intestinal peptide.
...
PMID:ARPP-21, a cAMP-regulated phosphoprotein enriched in dopamine-innervated brain regions: tissue distribution and regulation of phosphorylation in rat brain. 196 23
ARPP-21
(cAMP-regulated phosphoprotein, Mr = 21,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis) is a phosphoprotein highly enriched in concentration in the neurons of the limbic striatum. It is likely a third messenger in the intracellular cascade of events following neuronal stimulation by first-messenger activators of the
adenylate cyclase
system, including dopamine via the D1 receptor.
ARPP-21
expression is restricted to telencephalic post-mitotic, post-migrational neurons, and its precise pattern of temporal and spatial expression makes it an attractive candidate for the study of transcriptional regulation of neuronal maturation. To define genomic regions likely to contain functional promoter elements, we isolated the murine
ARPP-21
gene. Primer extension and T2 RNase protection analyses identified multiple transcription start sites, but 1.3 kb of 5'-flanking DNA revealed few consensus transcription factor binding sequences. A series of transient transfection assays in clonal cell lines which do not express
ARPP-21
identified a basal promoter active in both neuronal and non-neuronal lines. Expression in all lines was decreased by the inclusion of regions further upstream, and extinguished by the inclusion of the first intron. Further analyses are likely to reveal cell specific regulatory sequences.
...
PMID:ARPP-21: murine gene structure and promoter identification of a neuronal phosphoprotein enriched in the limbic striatum. 886 51
