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The Type and the Localization of cAMP-dependent Protein Kinase Regulate Transmission of cAMP Signals to the Nucleus in Cortical and Cerebellar Granule Cells
- Source :
- Journal of Biological Chemistry. 274:6546-6552
- Publication Year :
- 1999
- Publisher :
- Elsevier BV, 1999.
-
Abstract
- cAMP signals are received and transmitted by multiple isoforms of cAMP-dependent protein kinases, typically determined by their specific regulatory subunits. In the brain the major regulatory isoform RIIbeta and the RII-anchor protein, AKAP150 (rat) or 75 (bovine), are differentially expressed. Cortical neurons express RIIbeta and AKAP75; conversely, granule cerebellar cells express predominantly RIalpha and RIIalpha. Cortical neurons accumulate PKA catalytic subunit and phosphorylated cAMP responsive element binding protein very efficiently into nuclei upon cAMP induction, whereas granule cerebellar cells fail to do so. Down-regulation of RIIbeta synthesis by antisense oligonucleotides inhibited cAMP-induced nuclear signaling in cortical neurons. Expression in cerebellar granule cells of RIIbeta and AKAP75 genes by microinjection of specific expression vectors, markedly stimulated cAMP-induced transcription of the lacZ gene driven by a cAMP-responsive element promoter. These data indicate that the composition of PKA in cortical and granule cells underlies the differential ability of these cells to transmit cAMP signals to the nucleus.
- Subjects :
- Gene isoform
CAMP Responsive Element Binding Protein
Cerebellum
Protein subunit
A Kinase Anchor Proteins
Biology
Biochemistry
AKAP
cAMP
Cyclic AMP
medicine
Animals
Protein Isoforms
PKA
Protein kinase A
Molecular Biology
Adaptor Proteins, Signal Transducing
Cell Nucleus
Cerebral Cortex
Neurons
Proteins
Cell Biology
Cyclic AMP-Dependent Protein Kinases
Molecular biology
neuron
Rats
Cell biology
medicine.anatomical_structure
biology.protein
Carrier Proteins
CREB1
Nucleus
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 274
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....f5069fdaf79c9b3e481ea7b89016c309