J Immunol 1998,
PMID: 9637525
Lens, S M; den Drijver, B F; Pötgens, A J; Tesselaar, K; van Oers, M H; van Lier, R A
To dissect intracellular pathways involved in B cell Ag receptor (BCR)-mediated and Fas-induced human B cell death, we isolated clones of the Burkitt lymphoma cell line Ramos with different apoptosis sensitivities. Selection for sensitivity to Fas-induced apoptosis also selected for clones with enhanced BCR death sensitivity and vice versa. In contrast, clones resistant to Fas-mediated apoptosis could still undergo BCR-induced cell death. Based on the functional phenotypes of these clones, we hypothesized that both receptor-induced apoptosis pathways are initially distinct but may eventually converge. Indeed, ligation of both Fas and BCR resulted in cleavage of the IL-1beta-converting enzyme/Ced-3-like protease caspase 3 and its substrates Ac-Asp-Glu-Val-Asp-aldehyde and poly(ADP-ribose) polymerase. Markedly, qualitative differences in the caspase 3 cleavage pattern induced by Fas or BCR ligation were observed; whereas Fas ligation generated caspase 3 cleavage products of 19/20 and 17 kDa, only the latter cleavage product was found upon BCR cross-linking. The caspase inhibitor Val-Ala-Asp-fluoromethylketone blocked both Fas- and BCR-mediated apoptosis, but differentially affected caspase 3 cleavage induced by either stimulus. Finally, overexpression of a Fas-associated death domain (FADD) dominant-negative mutant protein was found to inhibit Fas-induced apoptosis but not BCR-induced apoptosis. Together our findings imply that Fas and BCR couple, via FADD-dependent and FADD-independent mechanisms, respectively, to distinct proteases upstream of caspase 3.
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Text Mining Data
caspase ⊣ BCR: "
Indeed, ligation of both Fas and
BCR resulted in cleavage of the IL-1beta converting enzyme/Ced-3-like protease
caspase 3 and its substrates Ac-Asp-Glu-Val-Asp-aldehyde and poly ( ADP-ribose ) polymerase
"
caspase ⊣ Fas: "
Indeed, ligation of both Fas and BCR resulted in cleavage of the IL-1beta converting enzyme/Ced-3-like protease caspase 3 and its substrates Ac-Asp-Glu-Val-Asp-aldehyde and poly ( ADP-ribose ) polymerase
"
Fas- ⊣ Val-Ala-Asp-fluoromethylketone: "
The caspase inhibitor Val-Ala-Asp-fluoromethylketone blocked both Fas- and BCR mediated apoptosis, but differentially affected caspase 3 cleavage induced by either stimulus
"
Manually curated Databases
No curated data.