(A) K-Raslox MEF cells transduced with retrovirus carrying doxycycline-inducible WT ARAF or the indicated mutants were grown in medium without or with 1 μM 4-OHT for a week to generate isogenic cells expressing or lacking K-RAS. Cells were then treated with 100 ng/ml doxycycline for 24 hours and subjected to western blot.
(B) K-Raslox MEF cells lacking K-RAS expression were transfected with indicated constructs and subjected to western blot.
(C and D) NIH3T3 cells expressing doxycycline-inducible RAF variants were treated with doxycycline for 48 hr. Signaling activity and RAS-GTP levels were then examined by western blot.
(E) NIH3T3 cells expressing doxycycline-inducible RAF variants were treated with 100 ng/ml doxycycline for 24 hours. Relative expression levels of ERK target genes were examined by qRT-PCR. Error bars, mean±SD triplicate of experiments.