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- W2073688909 abstract "Evidence is presented that distinct cellular signal transduction pathways involving cAMP-dependent protein kinase-A and phorbol ester-stimulated protein kinase-C coordinately modulate gene transcription through common as well as distinct cis-acting elements and DNA-binding proteins. When transfected and expressed in HeLa and placental JEG-3 cells, fusion reporter plasmids that differ only by a single base deletion or addition to interconvert the octameric cAMP-responsive element TGACGTCA (CRE) to form the heptameric phorbol ester-responsive element TGACTCA (TRE) are differentially regulated by cAMP and phorbol esters [12-O-tetradecanoyl phorbol- 14-acetate (TPA)]. Transcription directed by the CRE is stimulated by cAMP and not TPA, although the basal expression mediated by this element in JEG-3 and HeLa cells is augmented by endogenous protein kinase-C activity. In contrast, TRE mediates transcriptional responses to both cAMP and TPA, and the two agents together give synergistic responses. Inhibition of cAMP-dependent protein kinase-A by expression of a minigene encoding a peptide inhibitor of A-kinase abolishes the response of TRE to cAMP alone as well as the cAMP-induced component of the synergistic response to treatment with both TPA and cAMP. Desensitization of the protein kinase-C dependent pathway by prolonged exposure of cells to phorbol esters eliminates the TPA-induced transcription by TRE and inhibits the TPA-induced component of the synergistic response to both cAMP and TPA. Therefore, both protein kinases, A and C, are involved in transcriptional activation by the TRE; the function of either kinase alone results in a moderate level of activity, but the combined results of both functionally stimulated kinases are synergistically positive. Electrophoretic mobility shift assays using whole extracts of JEG-3 cells indicate that a common factors) binds both TRE and CRE; however, another factor(s) that binds to the CRE will not bind to the TRE. Further, a latent regulatory enhancer element (URE) located upstream of the CRE's in the human α gonadotropin gene, although inactive when paired alone with the α 100 promoter, induces basal andstimulated transcriptional activity of both CRE and TRE on the average of 10- to 20-fold. The data support the existence of a gene regulatory network consisting of related cis-acting elements and DNA-binding proteins whose transcriptional activities are regulated by the convergent actions of protein kinases-C and -A." @default.
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- W2073688909 date "1989-05-01" @default.
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- W2073688909 title "Distinct Adenosine 3′,5′-Monophosphate and Phorbol Ester-Responsive Signal Transduction Pathways Converge at the Level of Transcriptional Activation by the Interactions of DNA-Binding Proteins" @default.
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- W2073688909 doi "https://doi.org/10.1210/mend-3-5-868" @default.
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