title: Involvement of protein kinase A in fibroblast growth factor-2-activated transcription.
abstract: Polypeptide growth factors activate common signal transduction pathways, yet they can induce transcription of different target genes. The mechanisms that control this specificity are not completely understood. Recently, we have described a fibroblast growth factor (FGF)-inducible response element, FiRE, on the syndecan-1 gene. In NIH 3T3 cells, the FiRE is activated by FGF-2 but not by several other growth factors, such as platelet-derived growth factor or epidermal growth factor, suggesting that FGF-2 activates signaling pathways that diverge from pathways activated by other growth factors. In this paper, we report that the activation of FiRE by FGF-2 requires protein kinase A (PKA) in NIH 3T3 cells. The PKA-specific inhibitor H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) blocked the FGF-2-induced activation of FiRE, the transcription of the syndecan-1 gene, and cell proliferation. Also, expression of a dominant-negative form of PKA inhibited the FGF-2-induced FiRE activation and the transcription of the syndecan-1 gene. The binding of activator protein-1 transcription-factor complexes, required for the activation of FiRE, was blocked by inhibition of PKA activity before FGF-2 treatment. In accordance with the growth factor specificity of FiRE, the activity of PKA was stimulated by FGF-2 but not by platelet-derived growth factor or epidermal growth factor. Furthermore, a portion of the PKA catalytic subunit pool was translocated to the nucleus by FGF-2. Noticeably, the total cellular cAMP concentration was not affected by FGF-2 stimulus. We propose that the FGF-2-selective transcriptional activation through FiRE is caused by the ability of FGF-2 to control PKA activity.
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Tykistökatu 6B, BioCity, FIN-20520 Turku, Finland.
authors.forename: J P
authors.initials: JP
authors.lastname: Pursiheimo
authors.forename: M
authors.initials: M
authors.lastname: Jalkanen
authors.forename: K
authors.initials: K
authors.lastname: Taskén
authors.forename: P
authors.initials: P
authors.lastname: Jaakkola
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D007546:Isoquinolines / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000032:analysis; D011509:Proteoglycans / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D013449:Sulfonamides; D053668:Syndecan-1; D053667:Syndecans; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D013449:Sulfonamides; D053668:Syndecan-1; D053667:Syndecans; D018808:Transcription Factor AP-1; D016222:Fibroblast Growth Factor 2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide