title: Membrane localization of cAMP-dependent protein kinase amplifies cAMP signaling to the nucleus in PC12 cells.
abstract: 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.
authors.affiliation: 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
authors.forename: S
authors.initials: S
authors.lastname: Cassano
authors.forename: A
authors.initials: A
authors.lastname: Gallo
authors.forename: V
authors.initials: V
authors.lastname: Buccigrossi
authors.forename: A
authors.initials: A
authors.lastname: Porcellini
authors.forename: R
authors.initials: R
authors.lastname: Cerillo
authors.forename: M E
authors.initials: ME
authors.lastname: Gottesman
authors.forename: E V
authors.initials: EV
authors.lastname: Avvedimento
mesh_terms: 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
chemical_list: 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