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• W2169377140 endingPage "2857" @default.
• W2169377140 startingPage "2849" @default.
• W2169377140 abstract "The mechanism by which activation of common signal transduction pathways can elicit cell-specific responses remains an important question in biology. To elucidate the molecular mechanism by which the Ras signaling pathway activates a cell-type-specific gene, we have used the pituitary-specific rat prolactin (rPRL) promoter as a target of oncogenic Ras and Raf in GH4 rat pituitary cells. Here we show that expression of either c-Ets-1 or the POU homeo-domain transcription factor GHF-1/Pit-1 enhance the Ras/Raf activation of the rPRL promoter and that coexpression of the two transcription factors results in an even greater synergistic Ras response. By contrast, the related GHF-1-dependent rat growth hormone promoter fails to respond to Ras or Raf, indicating that GHF-1 alone is insufficient to mediate the Ras/Raf effect. Using amino-terminal truncations of c-Ets-1, we have mapped the c-Ets-1 region required to mediate the optimal Ras response to a 40-amino-acid segment which contains a putative mitogen-activated protein kinase site. Finally, dominant-negative Ets and GHF constructs block Ras activation of the rPRL promoter, and each blocks the synergistic activation mediated by the other partner protein, further corroborating that a functional interaction between c-Ets-1 and GHF-1 is required for an optimal Ras response. Thus, the functional interaction of a pituitary-specific transcription factor, GHF-1, with a widely expressed nuclear proto-oncogene product, c-Ets-1, provides one important molecular mechanism by which the general Ras signaling cascade can be interpreted in a cell-type-specific manner." @default.
• W2169377140 created "2016-06-24" @default.
• W2169377140 creator A5012080007 @default.
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• W2169377140 date "1995-05-01" @default.
• W2169377140 modified "2023-10-12" @default.
• W2169377140 title "Functional Interaction of c-Ets-1 and GHF-1/Pit-1 Mediates Ras Activation of Pituitary-Specific Gene Expression: Mapping of the Essential c-Ets-1 Domain" @default.
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• W2169377140 doi "https://doi.org/10.1128/mcb.15.5.2849" @default.
• W2169377140 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/230516" @default.
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