![]() ![]() ![]() Taken together these data demonstrate that the initiator caspase-8 can directly activate pro-caspase-3 without the requirement for an accelerator. ![]() Moreover, immunodepletion of a putative intermediary in the pathway to activation, pro-caspase-9, was without consequence. The pattern and rate of caspase-8 induced activation of pro-caspase-3 in cytosolic extracts was the same as in a purified system. Differentially processed forms of caspase-3 that accumulate during its activation have similar rates of activation, activities, and specificities. These rates are of sufficient magnitude to indicate direct processing in vivo. We show here that in a purified system, the initiator caspases-8 and -10 directly process the executioner pro-caspase-3 with activation rates ( k cat/ K m) of 8.7 × 10 5 and 2.8 × 10 5 m −1 s −1, respectively. The apoptotic signal triggered by ligation of members of the death receptor family is promoted by sequential activation of caspase zymogens. ![]()
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