title: Activation of protein kinase A by dibutyryl cAMP treatment of NIH 3T3 cells inhibits proliferation but fails to induce Ser-133 phosphorylation and transcriptional activation of CREB.
abstract: The cAMP analogue dibutyryl cAMP (dbcAMP) is often used to activate the protein kinase A pathway and to study the expression of cAMP-responsive genes. Here we show that in NIH 3T3 cells dbcAMP is able to activate PKA, but fails to stimulate expression of the cAMP-inducible c-fos gene. Co-expression of A-kinase anchoring protein 75, previously shown to amplify cAMP signalling and to stimulate c-fos expression, could not restore cAMP responsiveness of the c-fos promoter. DbcAMP-induced activation of PKA may result in poor translocation of the catalytic sub-units of PKA to the nucleus, indicated by the lack of both Ser-133 phosphorylation of the cAMP-response element binding factor CREB and stimulation of the transcriptional activity of this factor. DbcAMP treatment, however, inhibited cell proliferation. These results suggest that cAMP-mediated inhibition of proliferation may be independent of translocation of the catalytic sub-units into the nucleus.
authors.affiliation: Department of Gene Biology, Institute of Medical Biology, University of Tromsø, Norway.
authors.forename: O M
authors.initials: OM
authors.lastname: Seternes
authors.forename: R
authors.initials: R
authors.lastname: Sørensen
authors.forename: B
authors.initials: B
authors.lastname: Johansen
authors.forename: U
authors.initials: U
authors.lastname: Moens
mesh_terms: D016475:3T3 Cells; D000818:Animals; D003994:Bucladesine / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D015533:Transcriptional Activation
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016760:Proto-Oncogene Proteins c-fos; D005576:Colforsin; D012694:Serine; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases