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- W2012180535 abstract "Signals from the T cell receptor (TCR) are important for activation, differentiation, and proliferation. Members of the B cell leukemia/lymphoma-2 (Bcl-2) family of proteins are critical regulators of T cell apoptosis. The proapoptotic members Bax (Bcl-2-associated X protein) and Bak (Bcl-2-antagonist/killer) prevent the accumulation of excess lymphocytes. Jones et al. investigated other roles for Bax and Bak in T cell physiology. The authors reconstituted irradiated recombination-activating gene-1 (RAG-1)-deficient mice, which are deficient in T cells, with bone marrow cells from Bax–/–, Bak–/– (DKO), or wild-type mice. TCR stimulation of DKO cells isolated from these chimeric mice resulted in defective activation and proliferation, as measured by flow cytometry and 3[H]-thymidine incorporation. Whereas TCR stimulation of DKO cells resulted in decreased concentration of intracellular Ca2+ ([Ca2+]i) compared with that in wild-type cells, Western blotting analysis showed that phosphorylation of phospholipase Cγ isoforms, which are downstream of TCR activation, was comparable in both cell types. Treatment of DKO CD4+ T cells with a cell-permeable inositol 1,4,5-trisphosphate (IP3)-ester induced lower [Ca2+]i than did treatment of wild-type cells, indicating that DKO cells have defective IP3-dependent Ca2+ release from endoplasmic reticulum (ER) stores. This defect was reversed by either retroviral-mediated expression of Bax or treatment of DKO cells with ionomycin, which allows influx of extracellular Ca2+. DKO T cells were also defective for TCR-stimulated production of reactive oxygen species compared with wild-type cells. Together, these data establish Bax and Bak as important regulators of T cell proliferation through controlling TCR-stimulated Ca2+ mobilization from the ER." @default.
- W2012180535 created "2016-06-24" @default.
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- W2012180535 date "2007-08-28" @default.
- W2012180535 modified "2023-10-14" @default.
- W2012180535 title "Playing on Both Sides of the Field" @default.
- W2012180535 doi "https://doi.org/10.1126/stke.4012007tw308" @default.
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