Linked Life Data

18424699

Source:http://linkedlifedata.com/resource/pubmed/id/18424699

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-4-21
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5805-15
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Lck-dependent tyrosine phosphorylation of diacylglycerol kinase alpha regulates its membrane association in T cells.
pubmed:affiliation
Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't