IGFIR-IC-induced cell death is blocked by a catalytic mutant of
pro-caspase-9. (A and B) 293T cells were
transfected with 2 μg of DNA consisting of either pcDNA3, 0.5 μg
pIGFR-IC + 1.5 μg pcDNA3, or 0.5 μg pIGFR-IC + 1.5 μg dominant
negative caspase-9 (pC9DN, in A) or dominant negative
caspase-7 (pC7DN, in B) expression constructs.
Forty-eight hours after transfection, dead cells were counted.
Asterisks denote a highly significant difference from the control as
determined by one-way ANOVA. In A, F
= 25.2, P = 0.0002 with P =
0.0001 for pIGFIR-IC (Bonferroni/Dunn posthoc test). In
B, F = 118.487,
P < 0.0001, with P < 0.0001
for pIGFIR-IC and pIGFIR-IC + pC7DN (Bonferroni/Dunn posthoc test).
Error bars represent the SEM from three independent experiments.
(C) Protein extracts from cells cotransfected with
pIGFR-IC wild type or mutants, as indicated, and FLAG-tagged C9DN
expression constructs were subjected to immunoprecipitation (IP) using
an anti-IGFIR polyclonal antibody. Immunoprecipitates then were
resolved by 15% SDS/PAGE, and Western blotting was performed by
using a mAb against the FLAG epitope to detect caspase-9. WCE =
whole-cell extract.