SYK and LYN mediate B-cell receptor-independent calcium-induced apoptosis in DT-40 lymphoma B-cells.
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.
Zhu
De-Min
DM
Department of Immunology, Parker Hughes Cancer Center Parker Hughes Institute, 2669 Patton Road, Roseville, St. Paul, MN 55113, USA.
Tibbles
Heather E
HE
Vassilev
Alexei O
AO
Uckun
Fatih M
FM
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology; D002118:Calcium / Q000502:physiology*; D002645:Chickens; D004792:Enzyme Precursors / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D015759:Ionomycin / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016393:Lymphoma, B-Cell / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D051076:Proto-Oncogene Proteins c-fyn; D011947:Receptors, Antigen, B-Cell; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000502:physiology*
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D015759:Ionomycin; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002118:Calcium