Abstract
Cooperation between calcineurin (CN)-NFATc and RAF-MEK-ERK signaling pathways is essential in thymocyte positive selection. It is known that the Regulators of Calcineurin (RCAN) proteins can act either facilitating or suppressing CN-dependent signaling events. Here, we show that RCAN genes are expressed in lymphoid tissues, and address the role of RCAN proteins in T cell development. Overexpression of human RCAN3 and RCAN1 can modulate T cell development by increasing positive selection-related surface markers, as well as the "Erk(hi) competence state" in double positive thymocytes, a characteristic molecular signature of positive selection, without affecting CN activity. We also found that RCAN1/3 interact with RAF kinases and CN in a non-exclusive manner. Our data suggests that the balance of RCAN interactions with CN and/or RAF kinases may influence T cell positive selection.
References
Aug 30, 1990·Nature·P S OhashiH Hengartner
Oct 8, 1999·Immunity·L Van ParijsD Baltimore
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Rick B VegaEric N Olson
Aug 20, 2003·Nature Immunology·Sandra RyeomFrank McKeon
Apr 14, 2004·Current Medicinal Chemistry·Sara Martínez-Martínez, Juan Miguel Redondo
Jun 11, 2004·Immunity·Christine J WilliamsKatia Georgopoulos
Jun 7, 2005·Archives of Biochemistry and Biophysics·Young-Jin ChoYasufumi Sato
Mar 7, 2006·Gene·Silvia CanaiderPierluigi Strippoli
May 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bastiano SannaJeffery D Molkentin
Oct 19, 2006·FEBS Letters·Sung-Young ShinKwang-Hyun Cho
Feb 3, 2007·Biochimica Et Biophysica Acta·M Carme MuleroMercè Pérez-Riba
Jun 28, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kelvin J A DaviesXavier Estivill
Sep 5, 2007·The European Journal of Neuroscience·Sílvia PortaMaria L Arbonés
Feb 5, 2009·The Journal of Biological Chemistry·Ma Carme MuleroMercè Pérez-Riba
Mar 11, 2009·Molecular and Cellular Biology·Sohum MehtaKyle W Cunningham
Sep 1, 2009·Biochimica Et Biophysica Acta·Jae Youn LeeKwang Chul Chung
Oct 20, 2010·Immunology and Cell Biology·Nathalie LabrecqueSylvie Lesage
Dec 1, 2010·Trends in Cell Biology·Huiming LiPatrick G Hogan
May 7, 2013·Journal of Medical Genetics·Katherine R MartinMelanie A Pritchard
Jun 5, 2013·Biochimica Et Biophysica Acta·Sergio Martínez-HøyerMercè Pérez-Riba
Jan 28, 2014·PloS One·Eva Serrano-CandelasMercè Pérez-Riba