Regulation of c-fos Expression by Voltage-Dependent Calcium Channels
The determination of cell function is mediated to a significant degree by dynamic alterations in the intracellular concentration of free calcium. To date, the study of the role of calcium as a second messenger has been largely confined to the analysis of rapid events triggered by this cation that mostly involve posttranslational modification. However, recently it has been recognized that agents that provoke an influx of calcium ions into PC12 cells elicit a rapid, transient, transcriptional activation of thefosprotooncogene (Morgan and Curran, 1986; Greenberget al., 1986). This has led to the proposition (Fig. 1) that c-fosis but one member of a family of cellular immediate-early genes that are induced following stimulation and that act to modulate the long-term responses of a cell. As c-fosencodes a nuclear protein (Curranet al., 1984), it is assumed that these inducible genes are themselves involved in the activation and/or repression of further sets of genes that are responsible for such phe nomena as plasticity, adaptation, long-term potentiation, etc. This study will elaborate the evidence for the involvement of calcium in the regulation of both c-fosexpression and the posttranslational modification of its protein product (Fos).
KeywordsPC12 Cell Nerve Growth Factor Calcium Channel Antagonist Extracellular Calcium Calmodulin Inhibitor
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