Phosphatidylinositol metabolism and polyoma-mediated transformation.

Phosphatidylinositol metabolism and polyoma-mediated transformation.
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磷脂酰肌醇代谢和多瘤介导的转化。

DOI:
10.1073/pnas.83.11.3624
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发表时间:
1986
影响因子:
11.1
通讯作者:
Cantley,L
Cantley,L
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kaplan,DR;Whitman,M;Schaffhausen,B;Raptis,L;Garcea,RL;Pallas,D;Roberts,TM;Cantley,L

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利用多瘤转化细胞和多瘤感染细胞,在体内和体外研究了多瘤中型肿瘤抗原(MTAg)对磷脂酰肌醇代谢的影响。感染转化能力强的多瘤病毒的细胞表现出肌醇磷脂和第二信使肌醇三磷酸水平的增加。来自MTAg转化细胞的MTAg或pp60c-src免疫沉淀物含有磷酸化磷脂酰肌醇和磷脂酰肌醇4-磷酸的活性。当MTAg的合成受到激素或重金属诱导剂的调节时,该活性与MTAg并行诱导。一类转化缺陷多瘤突变体的免疫沉淀在体外具有相关的磷脂酰肌醇激酶活性水平降低,但能够以与野生型病毒相当的速率在外源蛋白质底物上磷酸化酪氨酸。因此,对于这些突变体,磷脂酰肌醇激酶活性比蛋白激酶活性与转化更紧密相关。这些结果表明,MTAg对磷脂酰肌醇代谢的改变在多瘤病毒转化中起作用。
The effect of polyoma middle-sized tumor antigen (MTAg) on phosphatidylinositol metabolism has been characterized in vivo and in vitro using polyoma-transformed and polyoma-infected cells. Cells infected with transformation-competent polyoma virus exhibit increased levels of inositol phospholipids and the second messenger inositol trisphosphate. MTAg or pp60c-src immunoprecipitates from MTAg-transformed cells contain an activity that phosphorylates phosphatidylinositol and phosphatidylinositol 4-phosphate. This activity is induced in parallel with MTAg when the MTAg synthesis is regulated by hormonal or heavy metal inducers. Immunoprecipitates from one class of polyoma mutants defective in transformation have a reduced level of associated phosphatidylinositol kinase activity in vitro yet are capable of tyrosine phosphorylation on exogenous protein substrates at rates comparable to wild-type virus. Thus, for these mutants, phosphatidylinositol kinase activity is more tightly correlated with transformation than is protein kinase activity. These results suggest that alterations in phosphatidylinositol metabolism by MTAg play a role in transformation by polyoma virus.