Signal transduction and gene control

Extracellular signals regulate gene expression by triggering signal transduction cascades that result in the modulation of transcription factor activity. This is most commonly achieved by changes in the phosphorylation state of these nuclear proteins. Phosphorylation affects transcription factor activity at several distinct levels. It can modulate their intracellular localization by controlling the association with other proteins, have both negative and positive effects on their DNA-binding activity, and modulate the activity of their transcriptional activation domains. In addition to phosphorylation, protein-protein interactions also have an important role in mediating a crosstalk at the nuclear level between different signalling pathways.