Regulation of urokinase expression in the developing avian heart: a role for the Ets-2 transcription factor
Abstract
During heart development, cells of the endocardial cushions undergo an epithelial-mesenchymal transformation and migrate into the surrounding extracellular matrix. This event is required for the normal formation of valves and chamber septation. Coincident with this phenotypic change is the expression of the serine protease urokinase by the mesenchymal cells. This protease plays an important role in remodeling of the matrix, promotion of cell migration by regulating cell-matrix interactions, and the activation of growth factors. To understand the mechanisms underlying the expression of urokinase during heart development, studies were designed to analyze the role of the Ets transcription factors in the regulation of the avian urokinase gene promoter. Deletion or mutagenesis of the Ets consensus sites significantly decreased the activity of the promoter in isolated cushion tissue cells. Proteins were identified by electrophoretic mobility shift analysis and UV-crosslinking which bound to a specific region of the promoter shown to be required for full transcriptional activity. Analyses based upon protein molecular weight and interaction with specific antibodies suggest a role for the Ets-2 protein in promoter binding and activity. ...Continue Reading
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