Regulation of cell death protease caspase-9 by phosphorylation
Regulation of cell death protease caspase-9 by phosphorylation
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DOI：
10.1126/science.282.5392.1318
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发表时间：
1998-11-13
期刊：
影响因子：
56.9
通讯作者：
Reed, JC
中科院分区：
文献类型：
--
作者：
Cardone, MH;Roy, N;Reed, JC
半胱氨酸天冬氨酸氨基转移酶是细胞内的一种蛋白水解酶，起着启动和促进细胞凋亡的作用。Akt和Akt激活剂p21-RAS可诱导细胞内caspase-9原(Pro-CASP9)的磷酸化。在表达活性RAS或Akt的细胞胞浆提取液中，细胞色素c诱导的原CASP9的蛋白降解过程存在缺陷。AKT在体外对丝氨酸-196上的重组CASP9进行磷酸化，并抑制其蛋白酶活性。突变的前CASP9(Ser196Ala)在体外和细胞内抵抗Akt介导的磷酸化和抑制，导致Akt耐药诱导细胞凋亡。因此，半胱氨酸天冬氨酸氨基转移酶可以被蛋白质磷酸化直接调节。
Caspases are intracellular proteases that function as initiators and effectors of apoptosis. The kinase Akt and p21-Ras, an Akt activator, induced phosphorylation of pro-caspase-9 (pro-Casp9) in cells. Cytochrome c-induced proteolytic processing of pro-Casp9 was defective in cytosolic extracts from cells expressing either active Ras or Akt. Akt phosphorylated recombinant Casp9 in vitro on serine-196 and inhibited its protease activity. Mutant pro-Casp9(Ser196Ala) was resistant to Akt-mediated phosphorylation and inhibition in vitro and in cells, resulting in Akt-resistant induction of apoptosis. Thus, caspases can be directly regulated by protein phosphorylation.