Cardone M H, Roy N, Stennicke H R, Salvesen G S, Franke T F, Stanbridge E, Frisch S, Reed J C
Program on Apoptosis and Cell Death Research, The Burnham Institute, La Jolla, CA 92037, USA.
Science. 1998 Nov 13;282(5392):1318-21. doi: 10.1126/science.282.5392.1318.
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.
半胱天冬酶是细胞内蛋白酶，作为细胞凋亡的启动子和效应器发挥作用。激酶Akt和Akt激活剂p21-Ras可诱导细胞中前半胱天冬酶-9（pro-Casp9）的磷酸化。在表达活性Ras或Akt的细胞的胞质提取物中，细胞色素c诱导的pro-Casp9的蛋白水解加工存在缺陷。Akt在体外使重组Casp9的丝氨酸-196位点磷酸化，并抑制其蛋白酶活性。突变型pro-Casp9（Ser196Ala）在体外和细胞中对Akt介导的磷酸化和抑制具有抗性，导致对Akt抗性的细胞凋亡诱导。因此，半胱天冬酶可通过蛋白质磷酸化直接调控。
