Lck-dependent tyrosine phosphorylation of diacylglycerol kinase alpha regulates its membrane association in T cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Ernesto MerinoIsabel Mérida

Abstract

TCR engagement triggers phospholipase Cgamma1 activation through the Lck-ZAP70-linker of activated T cell adaptor protein pathway. This leads to generation of diacylglycerol (DAG) and mobilization of intracellular Ca(2+), both essential for TCR-dependent transcriptional responses. TCR ligation also elicits transient recruitment of DAG kinase alpha (DGKalpha) to the lymphocyte plasma membrane to phosphorylate DAG, facilitating termination of DAG-regulated signals. The precise mechanisms governing dynamic recruitment of DGKalpha to the membrane have not been fully elucidated, although Ca(2+) influx and tyrosine kinase activation were proposed to be required. We show that DGKalpha is tyrosine phosphorylated, and identify tyrosine 335 (Y335), at the hinge between the atypical C1 domains and the catalytic region, as essential for membrane localization. Generation of an Ab that recognizes phosphorylated Y335 demonstrates Lck-dependent phosphorylation of endogenous DGKalpha during TCR activation and shows that pY335DGKalpha is a minor pool located exclusively at the plasma membrane. Our results identify Y335 as a residue critical for DGKalpha function and suggest a mechanism by which Lck-dependent phosphorylation and Ca(2+) elevation ...Continue Reading

References

Jan 1, 1986·Annual Review of Immunology·A WeissJ Stobo
Jun 20, 1995·Proceedings of the National Academy of Sciences of the United States of America·I JoungJ Shin
Jan 1, 1997·Critical Reviews in Immunology·M J Berridge
Jan 23, 1998·The International Journal of Biochemistry & Cell Biology·F Sakane, H Kanoh
Apr 17, 1999·The Journal of Biological Chemistry·M K Topham, S M Prescott
Jun 22, 1999·Current Opinion in Immunology·J E van Leeuwen, L E Samelson
Jan 29, 2000·Molecular and Cellular Biology·M F DennyD B Straus
Nov 18, 2000·Cellular Signalling·W J van Blitterswijk, B Houssa
Mar 29, 2001·Nature Immunology·S FeskeA Rao
Apr 4, 2001·The Journal of Cell Biology·M A SanjuánI Mérida
Mar 29, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·David R JonesIsabel Mérida
May 3, 2002·Immunology·Doreen A Cantrell
Jun 28, 2002·Cell·Fernando MaciánAnjana Rao
Aug 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Maximilian DiehnPatrick O Brown
Sep 18, 2002·The EMBO Journal·Youjia CaoRobert T Abraham
Dec 18, 2002·The Biochemical Journal·Tomas Mustelin, Kjetil Taskén
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miguel A SanjuánIsabel Mérida
Jul 2, 2003·The Journal of Biological Chemistry·Angel CiprésIsabel Mérida
Jul 29, 2003·Nature Immunology·Xiao-Ping ZhongGary A Koretzky
Jan 7, 2004·The Journal of Biological Chemistry·Lindsay DavidsonStuart Maudsley
Mar 19, 2005·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Rika Fukunaga-TakenakaNaoaki Saito
Aug 6, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jon C D HoutmanLawrence E Samelson
Oct 8, 2005·The Journal of Biological Chemistry·Shin-ichi ImaiFumio Sakane
Nov 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Trond MethiKjetil Tasken
Oct 10, 2006·Nature Immunology·Benjamin A OlenchockXiao-Ping Zhong
Oct 10, 2006·Nature Immunology·Yuanyuan ZhaThomas F Gajewski

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Citations

Oct 16, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tiantian LuoZhigang Guo
Feb 7, 2017·Immunology and Cell Biology·Antonia Ávila-FloresIsabel Mérida
Mar 28, 2013·International Journal of Molecular Sciences·Rohan P Joshi, Gary A Koretzky
Nov 4, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gianluca BaldanziAndrea Graziani
Apr 9, 2014·Journal of Biomedical Science·Yasuhito Shirai, Naoaki Saito
Mar 18, 2009·Immunological Reviews·Sharon A Matthews, Doreen A Cantrell
Aug 15, 2012·Molecular and Cellular Biology·Mónica Martínez-MorenoAntonia Ávila-Flores
Nov 24, 2019·International Journal of Molecular Sciences·Poojitha SitaramMatthew J Riese
Mar 25, 2018·Cancer Immunology, Immunotherapy : CII·Javier Arranz-NicolásAntonia Ávila-Flores
Dec 15, 2016·Frontiers in Cell and Developmental Biology·Gianluca BaldanziAndrea Graziani
Apr 11, 2021·Cancer Immunology, Immunotherapy : CII·Javier Arranz-NicolásIsabel Merida
Jun 3, 2021·International Journal of Molecular Sciences·Suresh VelnatiGianluca Baldanzi
Jun 19, 2009·Advances in Enzyme Regulation·Isabel MéridaPedro Torres-Ayuso
Apr 15, 2009·Biochimica Et Biophysica Acta·Matthew K Topham, Richard M Epand
Oct 19, 2011·Advances in Biological Regulation·Y ShiraiN Saito

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