The catalytic subunit of phosphoinositide 3-kinase: Requirements for oncogenicity
The catalytic subunit of phosphoinositide 3-kinase: Requirements for oncogenicity
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DOI：
10.1074/jbc.275.9.6267
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发表时间：
2000-03-03
影响因子：
4.8
通讯作者：
Vogt, PK
中科院分区：
文献类型：
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作者：
Aoki, M;Schetter, C;Vogt, PK
禽肉瘤病毒16（ASV 16）的逆转录病毒癌基因p3 k（v-p3 k）编码磷酸肌醇（PI）3-激酶的催化亚基p110 α。v-P3 k蛋白在体内和体外都是致癌的，它的细胞对应物c-P3 k缺乏致癌性，病毒Gag序列与c-P3 k氨基末端的融合激活了转化潜力，激活也可以通过在c-P3 k氨基末端添加肉豆蔻基化信号或在羧基末端添加法尼基化信号来实现，突变的肉豆蔻基化信号同样有效;它还引起P3 k激酶活性的强烈增加。抑制脂质激酶活性的突变消除致癌性。P3 k的转化活性与诱导Akt活化磷酸化的能力相关。P3 k的点突变和氨基端缺失与P3 k的致瘤活性无关，P3 k与PI 3-激酶调节亚基p85或Pas的相互作用不是转化所必需的。这些结果支持了P3 k的致瘤性依赖于组成性脂激酶活性的结论。Akt是P3 k致癌信号的重要且可能是必需的下游组分。
The retroviral oncogene p3k (v-p3k) of avian sarcoma virus 16 (ASV16) codes for the catalytic subunit of phosphoinositide (PI) 3-kinase, p110 alpha. The v-P3k protein is oncogenic in vivo and in vitro; its cellular counterpart, c-P3k, lacks oncogenicity, Fusion of viral Gag sequences to the amino terminus of c-P3k activates the transforming potential, Activation can also be achieved by the addition of a myristylation signal to the amino terminus or of a farnesylation signal to the carboxyl terminus of c-P3k, A mutated myristylation signal was equally effective; it also caused a strong increase in the kinase activity of P3k, Mutations that inactivate lipid kinase activity abolish oncogenicity, The transforming activity of P3k is correlated with the ability to induce activating phosphorylation in Akt. Point mutations and amino-terminal deletions recorded in v-P3k were shown to be irrelevant to the activation of oncogenic potential, Interactions of P3k with the regulatory subunit of PI 3-kinase, p85, or with Pas are not required for transformation, These results support the conclusion that the oncogenicity of P3k depends on constitutive lipid kinase activity. Akt is an important and probably essential downstream component of the oncogenic signal from P3k.