English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/3680
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Lck-Dependent Tyrosine Phosphorylation of Diacylglycerol Kinase {alpha} Regulates Its Membrane Association in T Cells

AuthorsMerino Plaza, Ernesto; Ávila Flores, Juana Antonia; Shiriai, Yasuhito; Moraga, Ignacio; Saito, Naoaki; Mérida, Isabel
Issue DateMay-2008
CitationJ Immunol. 2008 May 1;180(9):5805-15
AbstractTCR 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 regulate DGKalpha membrane localization. The concerted action of these two signals results in transient, receptor-regulated DGKalpha relocalization to the site at which it exerts its function as a negative modulator of DAG-dependent signals.
ISBNPMID: 18424699
Appears in Collections:(CNB) Artículos
Files in This Item:
File Description SizeFormat 
proof-3.pdf711,15 kBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.