A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT

Nature
Yousang GwackAnjana Rao

Abstract

Precise regulation of the NFAT (nuclear factor of activated T cells) family of transcription factors (NFAT1-4) is essential for vertebrate development and function. In resting cells, NFAT proteins are heavily phosphorylated and reside in the cytoplasm; in cells exposed to stimuli that raise intracellular free Ca2+ levels, they are dephosphorylated by the calmodulin-dependent phosphatase calcineurin and translocate to the nucleus. NFAT dephosphorylation by calcineurin is countered by distinct NFAT kinases, among them casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3). Here we have used a genome-wide RNA interference (RNAi) screen in Drosophila to identify additional regulators of the signalling pathway leading from Ca2+-calcineurin to NFAT. This screen was successful because the pathways regulating NFAT subcellular localization (Ca2+ influx, Ca2+-calmodulin-calcineurin signalling and NFAT kinases) are conserved across species, even though Ca2+-regulated NFAT proteins are not themselves represented in invertebrates. Using the screen, we have identified DYRKs (dual-specificity tyrosine-phosphorylation regulated kinases) as novel regulators of NFAT. DYRK1A and DYRK2 counter calcineurin-mediated dephosphorylation of NFAT1 b...Continue Reading

References

Mar 28, 1997·Science·C R BealsG R Crabtree
Jan 25, 2000·The Journal of Biological Chemistry·S HimpelW Becker
Mar 24, 2000·Science·E W MyersJ C Venter
Nov 7, 2000·The Journal of Biological Chemistry·J W Neal, N A Clipstone
Feb 27, 2003·Biochemical and Biophysical Research Communications·Stephan WiechmannWalter Becker
Apr 3, 2003·Nature Reviews. Molecular Cell Biology·Ernesto Carafoli
Aug 23, 2003·Genes, Brain, and Behavior·A Bhattacharyya, C N Svendsen
Sep 17, 2003·Genes & Development·Patrick G HoganAnjana Rao
Dec 19, 2003·Current Biology : CB·H Llewelyn Roderick, Martin D Bootman
Jan 28, 2004·The Journal of General Physiology·Andriy V YerominMichael D Cahalan
Feb 7, 2004·Science·Michael BoutrosUNKNOWN Heidelberg Fly Array Consortium
May 4, 2004·Molecular and Cellular Biology·Heidi OkamuraAnjana Rao
Jul 27, 2004·Protein Science : a Publication of the Protein Society·Natarajan Kannan, Andrew F Neuwald
Jan 13, 2005·Methods in Enzymology·Susan ArmknechtNorbert Perrimon
May 4, 2005·The Journal of Cell Biology·Jack RoosKenneth A Stauderman
Jul 12, 2005·Current Biology : CB·Jen LiouTobias Meyer

❮ Previous
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Citations

Mar 6, 2007·Pflügers Archiv : European journal of physiology·Magali SavignacJose R Naranjo
Mar 14, 2013·Molecules and Cells·Sonal Srikanth, Yousang Gwack
Mar 21, 2012·Cell Research·Zhihua Liu, Michael J Lenardo
Dec 25, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Fleur C AubartJean-Sébastien Hulot
Mar 17, 2009·Nature Cell Biology·Subbareddy Maddika, Junjie Chen
Oct 29, 2010·Nature Communications·Yasushi OgawaMasatoshi Hagiwara
Jul 22, 2009·Nature Immunology·Sonia Sharma, Anjana Rao
Aug 23, 2006·Nature Immunology·Sara Cherry, Neal Silverman
Oct 24, 2009·Nature Reviews. Cancer·Maria Mancini, Alex Toker
Aug 21, 2010·Nature Reviews. Immunology·Martin R Müller, Anjana Rao
Aug 16, 2008·Molecular BioSystems·Richelle Sopko, Brenda J Andrews
Jun 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yukiko KurodaKatsuhiko Mikoshiba
Apr 9, 2009·Proceedings of the National Academy of Sciences of the United States of America·Martin R MüllerAnjana Rao
Aug 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Srimoyee GhoshMartin R Müller
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sonia SharmaAnjana Rao
Apr 18, 2009·The Journal of Biological Chemistry·Christian KuhnNorbert Frey
Oct 6, 2009·The Journal of Biological Chemistry·Youngkyun LeeHong-Hee Kim
Dec 8, 2009·The Journal of Biological Chemistry·Naoe TairaKiyotsugu Yoshida
Aug 11, 2010·The Journal of Biological Chemistry·Joongkyu ParkKwang Chul Chung
Jan 22, 2011·The Journal of Biological Chemistry·Mei LuXiulian Sun
Feb 2, 2011·The Journal of Biological Chemistry·Gregory L SzetoJanice E Clements
Oct 4, 2011·The Journal of Biological Chemistry·Min-Su JungSul-Hee Chung
Apr 13, 2012·The Journal of Biological Chemistry·Atsushi KoikeTakayoshi Kuno
Sep 15, 2012·The Journal of Biological Chemistry·Jason D UlrichYuriy M Usachev
Jan 9, 2013·The Journal of Biological Chemistry·Donald R WalkinshawXiang-Jiao Yang
Oct 16, 2008·The Journal of Biological Chemistry·Olga BogachevaDon M Wojchowski
Jan 19, 2007·Molecular Biology of the Cell·Mónica AlvarezSusana de la Luna
Dec 3, 2009·Briefings in Functional Genomics·Jaakko Mattila, Oscar Puig
Jul 15, 2011·Briefings in Functional Genomics·Chris Bakal
Jan 24, 2012·Cardiovascular Research·Paula A Da Costa Martins, Leon J De Windt
Mar 20, 2009·Human Molecular Genetics·Frances K WisemanElizabeth M C Fisher
Aug 11, 2012·Journal of Molecular Cell Biology·Moisés PérezMarco A Calzado
Apr 8, 2011·Nucleic Acids Research·Wei QianFei Liu
Jul 10, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Olivier DésyPedro O de Campos-Lima
May 30, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Fei LiuCheng-Xin Gong
Mar 27, 2007·Cold Spring Harbor Symposia on Quantitative Biology·B Mathey-Prevot, N Perrimon
Dec 26, 2008·Science Signaling·Gerald R Crabtree, Isabella A Graef
Apr 7, 2010·Annual Review of Biochemistry·Stephanie MohrNorbert Perrimon

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