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Purinergic Signalling

, 3:59

First Online: 03 January 2007Received: 22 February 2006Accepted: 13 March 2006DOI: 10.1007-s11302-006-9037-8

Cite this article as: Armstrong, S., Korcok, J., Sims, S.M. et al. Purinergic Signalling 2007 3: 59. doi:10.1007-s11302-006-9037-8


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-κB 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-κB 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.

Key wordsAP-1 CREB mast cell microglia NFAT NF-κB osteoclast P2 receptor STAT T-cell AbbreviationsAP-1activator protein 1

ATFactivating transcription factor



CaM kinaseCa-calmodulin-dependent protein kinase

CBPCREB-binding protein

ChIPchromatin immunoprecipitation


CREcyclic AMP-response element

CREBCRE binding protein

EMSAelectrophoretic mobility shift assay

ERKextracellular signal-regulated kinase

IκBinhibitor of NF-κB


iNOSinducible nitric oxide synthase

JAKJanus kinase


MAP kinasemitogen-activated protein kinase

MEKMAP kinase-ERK kinase

NFATnuclear factor of activated T-cells

NF-κBnuclear factor κB

RSK2ribosomal S6 kinase 2

STATsignal transducer and activator of transcription

TNF-αtumor necrosis factor-α

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Autor: Souzan Armstrong - Jasminka Korcok - Stephen M. Sims - S. Jeffrey Dixon


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