Signal transduction studies on single cell level: P38, but not NFATc2, is the main regulator of NFATc1/A expression in human Th cells
© Bendfeldt et al; licensee BioMed Central Ltd. 2009
Published: 26 February 2009
NFATc2 and NFATc1 are the most prominent NFAT factors in T helper (Th) cells. They overlap in their functions for cytokine expression and were commonly activated by T-cell receptor (TcR)/calcium/calcineurin signaling pathway. However, they differ strikingly in their mode of expression. NFATc2 is constitutively expressed in Th cells, whereas the NFATc1/A, the most prominent NFATc1 isoform in Th cells, is strongly induced by antigen-specific stimulation of T-cell receptor (TcR) and co-receptor(s).
The regulation of NFATc1/A expression is controversially discussed. Single cell analysis of activated transcription factors and signaling molecules enabled us to show that the activated kinase p38 is the main component for NFATc1/A induction. Using specific inhibitors and the existing different modes of activation of signaling pathways we could rule out that activated NFATc2 and NF-kB play a prominent role in regulating NFATc1/A expression. Furthermore, we clearly demonstrated that NFATc1/A induction does not exhibit a switch-like dependence on calcineurin/NFATc2 activity.
In general, our data and results confirmed the relevance and importance to study cell signaling on single cell level.
This article is published under license to BioMed Central Ltd.