MOUSE LYMPHOMA-CELLS DESTINED TO UNDERGO APOPTOSIS IN RESPONSE TO THAPSIGARGIN TREATMENT FAIL TO GENERATE A CALCIUM-MEDIATED GRP78 GRP94 STRESS-RESPONSE/

grp78/grp94 induction is critical for maintaining the viability of epi thelial cells and fibroblasts following treatment with thapsigargin (T G), an inhibitor of Ca2+ uptake into the endoplasmic reticulum, In con trast to these cell types, WEHI7.2 mouse lymphoma cells undergo apopto sis when treated with TG, prompting us to examine the grp78/grp94 stre ss response in WEHI7.2 cells, TG treatment failed to induce grp78/grp9 4 transcription in WEHI7.2 cells, measured by Northern hybridization a nd nuclear run-on assays, even if the cells were protected from apopto sis by overexpressing bcl-2. However, grp78/grp94 transcription was in duced by the glycosylation inhibitor tunicamycin, suggesting that ther e are at least two grp78/grp94 signaling pathways, one in response to TG-induced endoplasmic reticulum Ca2+ pool depletion, which is inopera ble in WEHI7.2 cells, and one in response to glycosylatian inhibition, which is operable in WEHI7.2 cells. Studies of additional lymphoid li nes, as well as several nonlymphoid lines, suggested a correlation bet ween grp78/grp94 induction and resistance to apoptosis following TG tr eatment, In conclusion, the vulnerability of TG-treated WEHI7.2 cells to apoptosis may be due to failure to signal a grp78/grp94 stress resp onse.