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Diacylglycerol kinase α activity promotes survival of CD4 + 8 + double positive cells during thymocyte development
Author(s) -
Outram Susan V.,
Crompton Tessa,
Merida Isabel,
Varas Alberto,
MartinezA Carlos
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01385.x
Subject(s) - diacylglycerol kinase , thymocyte , second messenger system , phosphatidic acid , biology , microbiology and biotechnology , t cell receptor , kinase , protein kinase c , population , t cell , signal transduction , biochemistry , immunology , medicine , phospholipid , immune system , environmental health , membrane
Summary The diacylglycerol kinases (DGK) form a family of isoenzymes that catalyse the conversion of diacylglycerol (DAG) to phosphatidic acid (PA), both powerful second messengers in the cell. DGKα is expressed in brain, peripheral T cells and thymocytes and has been shown to translocate to the nuclear matrix upon T‐cell receptor (TCR) engagement. Here, we show that high level expression of DGKα is induced following a signal transmitted through the pre‐TCR and the protein tyrosine kinase, lck. Activity of DGKα contributes to survival in CD4 + 8 + (DP) thymocytes as pharmacological inhibition of DGK activity results in death of this cell population both in cell suspension and thymic explants. DGKα promotes survival in these thymocytes through a Bcl‐regulated pathway. A consequence of inhibition of DGKα is the specific down‐regulation of Bcl‐xl, whereas in transgenic mice that over‐express Bcl‐2, death induced by the inhibitor is partially blocked. Thus we report a novel activity of DGKα in survival of thymocytes immediately after entry into the DP stage in development.