Membrane localization of cAMP-dependent protein kinase amplifies cAMP signaling to the nucleus in PC12 cells.
The A126 cell line, in contrast to its PC12 parent, does not differentiate, accumulate nuclear cAMP-dependent protein kinase A (PKA) catalytic subunit, or transcribe cAMP-dependent promoters in response to cAMP. Total PKA is reduced by 50% and is partly resistant to cAMP-induced dissociation in vivo. Unlike PC12, where PKAII is membrane-associated, PKAII is exclusively cytosolic in A126. Cotransfection with the RII anchor protein (AKAP75) and the PKA catalytic subunit (C-PKA) restored cAMP-induced transcription to levels found in PC12. These data indicate that membrane-bound PKAII amplifies cAMP signaling to the nucleus and suggest that cAMP-mediated responses are specified by the type and cellular localization of the PKA isoform.
Cassano
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S
Centro di Endocrinologia ed Oncologia Sperimentale del CNR, c/o Dipartimento di Biologia e Patologia Molecolare e Cellulare, Facoltà di Medicina, Università "Federico II" 80131 Napoli, Italy. Avvedim@cds.unina.it
Gallo
A
A
Buccigrossi
V
V
Porcellini
A
A
Cerillo
R
R
Gottesman
M E
ME
Avvedimento
E V
EV
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000235:genetics; D051381:Rats; D015398:Signal Transduction
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C415703:Akap5 protein, rat; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D011506:Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases