Activation of transcription factors by extracellular nucleotides in immune and related cell types

Extracellular nucleotides, acting through P2 receptors, can regulate gene expression via intracellular signaling pathways that control the activity of transcription factors. Relatively little is known about the activation of transcription factors by nucleotides in immune cells. The NF-kappaB family of transcription factors is critical for many immune and inflammatory responses. Nucleotides released from damaged or stressed cells can act alone through certain P2 receptors to alter NF-kappaB activity or they can enhance responses induced by pathogen-associated molecules such as LPS. Nucleotides have also been shown to regulate the activity of other transcription factors (AP-1, NFAT, CREB and STAT) in immune and related cell types. Here, we provide an overview of transcription factors shown to be activated by nucleotides in immune cells, and describe what is known about their mechanisms of activation and potential functions. Furthermore, we propose areas for future work in this new and expanding field.