INDUCTION OF NFAT-MEDIATED TRANSCRIPTION BY G(Q)-COUPLED RECEPTORS INLYMPHOID AND NONLYMPHOID CELLS

The nuclear factor of activated T cells (NFAT) was discovered as an in ducible transcription factor activated by antigen stimulation of the T cell receptor in lymphocytes. Stimulation of NFAT-mediated transcript ion is now reported in both lymphoid and non-lymphoid cells following activation of a neurotransmitter receptor. Carbachol induces robust lu ciferase responses in Jurkat and pheochromocytoma PC12 cells expressin g an NFAT-luciferase reporter construct and a G(q)-coupled m3 muscarin ic receptor. Cyclosporin blocks this response in PC12 cells, as in Jur kat cells. In PC12 cells expressing a G(i)-coupled m2 muscarinic recep tor, carbachol induces NFAT-mediated luciferase activity that is stric tly dependent upon co-expression of a chimeric G alpha(q)/alpha(i) sub unit which confers G(q)-effector coupling on G(i)-linked receptors/ Th ese findings suggest that neurotransmitters, autacoids, or hormones ac ting on G(q)-protein-coupled receptors may serve as physiological stim ulators of NFAT in lymphoid and non lymphoid cells.