1. SYK and LYN Mediate B-cell Receptor-independent Calcium-induced Apoptosis in DT-40 Lymphoma B-cells
- Author
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Heather E. Tibbles, De-Min Zhu, Alexei O. Vassilev, and Fatih M. Uckun
- Subjects
Cancer Research ,Lymphoma, B-Cell ,B-cell receptor ,Ionophore ,Receptors, Antigen, B-Cell ,Syk ,chemistry.chemical_element ,Apoptosis ,Calcium ,Proto-Oncogene Proteins c-fyn ,chemistry.chemical_compound ,immune system diseases ,LYN ,Proto-Oncogene Proteins ,hemic and lymphatic diseases ,Agammaglobulinaemia Tyrosine Kinase ,Tumor Cells, Cultured ,medicine ,Animals ,Syk Kinase ,B-Lymphocytes ,Enzyme Precursors ,Chemistry ,Ionomycin ,Intracellular Signaling Peptides and Proteins ,Hematology ,Protein-Tyrosine Kinases ,medicine.disease ,Lymphoma ,src-Family Kinases ,Oncology ,Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ,Cancer research ,Chickens - Abstract
Here, we report that the calcium ionophore ionomycin induces a massive Ca2+-dependent apoptosis in wildtype DT-40 chicken B lymphoma cells, as well as in BTK-deficient, PLCgamma2-deficient and IP3 receptor-deficient DT-40 cells, but not in LYN- or SYK-deficient DT-40 cells. Notably, the deficiency of CSK, a negative regulator of Src-family PTK, promoted ionomycin-induced apoptosis of DT-40 cells. Reconstitution of SYK-deficient cells with wild-type SYK restored the apoptotic response of the cells to ionomycin, but the expression of FYN or LCK in LYN-deficient cells did not restore the apoptotic response of LYN-deficient cells. Taken together, our data suggests that both LYN and SYK, but not BTK, FYN or LCK, are crucial mediators of BCR-independent Ca2+-induced apoptosis in DT-40 lymphoma B cells.
- Published
- 2002