The type and the localization of cAMP-dependent protein kinase regulate transmission of cAMP signals to the nucleus in cortical and cerebellar granule cells.
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.
Istituto di Farmacologia, Facoltà di Farmacia, Università di Pavia, Italy.
M
M
Paolillo
A
A
Feliciello
A
A
Porcellini
C
C
Garbi
M
M
Bifulco
S
S
Schinelli
C
C
Ventra
E
E
Stabile
G
G
Ricciardelli
G
G
Schettini
E V
EV
Avvedimento
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins; D002467:Cell Nucleus / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C415703:Akap5 protein, rat; D002352:Carrier Proteins; D020033:Protein Isoforms; D011506:Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases