Induction of NFAT-mediated transcription by G(q)-coupled receptors in lymphoid and non-lymphoid cells

The nuclear factor of activated T cells (NFAT) was discovered as an inducible transcription factor activated by antigen stimulation of the T cell receptor in lymphocytes. Stimulation of NFAT-mediated transcription is now reported in both lymphoid and non-lymphoid cells following activation of a neurotransmitter receptor. Carbachol induces robust luciferase responses in Jurkat and pheochromocytoma PC12 cells expressing an NFAT-luciferase reporter construct and a G(q)-coupled m3 muscarinic receptor. Cyclosporin blocks this response in PC12 cells, as in Jurkat cells. In PC12 cells expressing a G(i)-coupled m2 muscarinic receptor, carbachol induces NFAT-mediated luciferase activity that is strictly dependent upon co-expression of a chimeric G alpha(q)/alpha(i) subunit which confers G(q)-effector coupling on G(i)-linked receptors/ These findings suggest that neurotransmitters, autacoids, or hormones acting on G(q)-protein-coupled receptors may serve as physiological stimulators of NFAT in lymphoid and non lymphoid cells.