Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1996-6-21
pubmed:abstractText
Proliferation of T lymphocytes is triggered by the interaction of interleukin 2 (IL-2) with its high affinity specific receptor that is expressed on the cell surface following T lymphocyte activation. Significant advances have recently been made in identifying the multiple signals that follow IL-2 receptor occupancy, although the exact mechanism responsible for IL-2-induced proliferation remains an enigma. It has been shown previously that unique species of phosphatidic acid are rapidly produced in vivo following IL-2 binding. It was then suggested that, in contrast to other eukaryotic growth factor systems, phosphatidic acid was at least in part generated through IL-2-induced diacylglycerol (DG) kinase activation. In the present study we demonstrate IL-2-dependent activation of the alpha isoform of DG kinase. Confocal microscopy studies reveal that the enzyme is located in the cytosol and nuclei of resting T cells. Interleukin 2 stimulation induces translocation of the enzyme to the perinuclear region. Furthermore, our results indicate that inhibition of the alpha isoform of DG kinase has a profound effect on IL-2-induced T cell growth. Studies on cell cycle distribution demonstrate that the inhibition of IL-2-induced phosphatidic acid production induces arrest in late G1 phase of IL-2 dependent cells. Altogether, these results link previous observations of interleukin 2 and phosphatidic acid production to activation of an specific isoform of DG kinase and suggest that activation of this enzyme is part of a novel signaling cascade that utilizes phosphatidic acid as an effector molecule.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10334-40
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8626603-Cell Compartmentation, pubmed-meshheading:8626603-Cell Cycle, pubmed-meshheading:8626603-Cells, Cultured, pubmed-meshheading:8626603-Diacylglycerol Kinase, pubmed-meshheading:8626603-Enzyme Activation, pubmed-meshheading:8626603-Enzyme Inhibitors, pubmed-meshheading:8626603-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:8626603-Humans, pubmed-meshheading:8626603-Interleukin-2, pubmed-meshheading:8626603-Lymphocyte Activation, pubmed-meshheading:8626603-Phosphatidic Acids, pubmed-meshheading:8626603-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:8626603-Pyrimidinones, pubmed-meshheading:8626603-Receptors, Interleukin-2, pubmed-meshheading:8626603-Signal Transduction, pubmed-meshheading:8626603-T-Lymphocytes, pubmed-meshheading:8626603-Thiazoles
pubmed:year
1996
pubmed:articleTitle
Phosphatidic acid generation through interleukin 2 (IL-2)-induced alpha-diacylglycerol kinase activation is an essential step in IL-2-mediated lymphocyte proliferation.
pubmed:affiliation
Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Campus de Cantoblanco, Madrid 28049, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't