Induction of NFAT-mediated transcription by Gq-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 Gq-coupled m3 muscarinic receptor. Cyclosporin blocks this response in PC12 cells, as in Jurkat cells. In PC12 cells expressing a Gi-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 Gq-effector coupling on Gi-linked receptors. These findings suggest that neurotransmitters, autacoids, or hormones acting on Gq-protein-coupled receptors may serve as physiological stimulators of NFAT in lymphoid and non-lymphoid cells.
Boss
V
V
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Talpade
D J
DJ
Murphy
T J
TJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016716:PC12 Cells; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D011976:Receptors, Muscarinic; D014157:Transcription Factors; D008156:Luciferases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium