PMID- 18424699
OWN - NLM
STAT- MEDLINE
DCOM- 20080604
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 180
IP  - 9
DP  - 2008 May 1
TI  - Lck-dependent tyrosine phosphorylation of diacylglycerol kinase alpha regulates 
      its membrane association in T cells.
PG  - 5805-15
AB  - 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 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.
FAU - Merino, Ernesto
AU  - Merino E
AD  - Department of Immunology and Oncology, Centro Nacional de Biotecnologia/Consejo 
      Superior de Investigaciones Cientificas, Madrid, Spain.
FAU - Avila-Flores, Antonia
AU  - Avila-Flores A
FAU - Shirai, Yasuhito
AU  - Shirai Y
FAU - Moraga, Ignacio
AU  - Moraga I
FAU - Saito, Naoaki
AU  - Saito N
FAU - Merida, Isabel
AU  - Merida I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - EC 2.7.1.107 (Diacylglycerol Kinase)
RN  - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck))
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
RN  - EC 2.7.10.2 (ZAP70 protein, human)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Calcium Signaling/*immunology
MH  - Cell Membrane/enzymology/genetics/*immunology
MH  - Diacylglycerol Kinase/genetics/*immunology/metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - Lymphocyte Activation/physiology
MH  - Lymphocyte Specific Protein Tyrosine Kinase 
      p56(lck)/genetics/*immunology/metabolism
MH  - Phospholipase C gamma/genetics/immunology/metabolism
MH  - Phosphorylation
MH  - Protein Structure, Tertiary/genetics
MH  - Receptors, Antigen, T-Cell/genetics/immunology/metabolism
MH  - T-Lymphocytes/enzymology/*immunology
MH  - ZAP-70 Protein-Tyrosine Kinase/genetics/immunology/metabolism
EDAT- 2008/04/22 09:00
MHDA- 2008/06/05 09:00
CRDT- 2008/04/22 09:00
PHST- 2008/04/22 09:00 [pubmed]
PHST- 2008/06/05 09:00 [medline]
PHST- 2008/04/22 09:00 [entrez]
AID - 180/9/5805 [pii]
AID - 10.4049/jimmunol.180.9.5805 [doi]
PST - ppublish
SO  - J Immunol. 2008 May 1;180(9):5805-15. doi: 10.4049/jimmunol.180.9.5805.