Membrane-bound cAMP-dependent protein kinase controls cAMP-induced differentiation in PC12 cells.
The A126 cell line, a derivative of PC12, is defective in cAMP-induced transcription and does not differentiate in the presence of cAMP. In these cells overexpression of a cAMP-dependent protein kinase (PKA) anchor protein, AKAP75, and of the PKA catalytic subunit substantially increased the fraction of PKAII bound to the membrane, stimulated the transcription of cAMP-induced genes, and induced terminal differentiation. Conversely, wild type PC12 cells expressing a derivative of the AKAP75 protein, AKAP45, which binds the PKA regulatory subunits RII, but fails to locate them to the membranes, induced translocation of PKAII to the cytosol. These cells did not efficiently accumulate PKA catalytic subunit in the nuclei when stimulated with cAMP, did not transcribe cAMP-induced genes, and failed to differentiate when exposed to cAMP. These data indicate that membrane-bound PKA positively controls the transcription of cAMP-induced genes and differentiation in PC12 cells.
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Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Molecolare e Cellulare, Facoltà di Medicina e Chirurgia, Università "Federico II" Napoli, 80131 Napoli, Italy.
Di Lieto
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Cerillo
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Avvedimento
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter; D008565:Membrane Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C415703:Akap5 protein, rat; D002352:Carrier Proteins; D008565:Membrane Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D020932:Nerve Growth Factor; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases