POLYOMA-VIRUS TRANSFORMING PROTEIN ASSOCIATES WITH THE PRODUCT OF THE C-SRC CELLULAR GENE

POLYOMA-VIRUS TRANSFORMING PROTEIN ASSOCIATES WITH THE PRODUCT OF THE C-SRC CELLULAR GENE
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DOI:
10.1038/303435a0
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发表时间:
1983-01-01
期刊:
影响因子:
64.8
通讯作者:
SMITH, AE
SMITH, AE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
COURTNEIDGE, SA;SMITH, AE

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多瘤病毒可以改变培养物中生长的啮齿动物细胞的生长特性,并在易感动物中形成肿瘤1,这种活性很大程度上归因于1-3一种病毒编码的蛋白质,称为中T。中T在体外具有相关的酪氨酸特异性蛋白激酶活性4-6,并与细胞膜相互作用7,但其转化能力的生化基础仍不清楚。尽管不同多瘤病毒突变体的转化活性与其在体外激酶反应中接受中间T酪氨酸磷酸的能力之间存在一定相关性4,但蛋白质中磷酸酪氨酸的丰度在多瘤病毒转化的细胞中并未升高8,并且尚未鉴定出推定激酶的细胞底物。目前尚不清楚中 T 的酪氨酸激酶是否是蛋白质本身的内在活性或相关酶的特性。这里描述的实验表明,中间 T 的一部分与细胞癌基因的产物 pp60c-src 形成稳定的复合物,并使我们提出,中间 T 相关激酶至少部分是 pp60c-srcrather 的特性,而不是中间 T 本身的特性。
Polyoma virus can transform the growth properties of rodent cells grown in culture and form tumours in susceptible animals1, an activity largely due1–3to one of the virus-encoded proteins, called middle T. Middle T has an associated tyrosine-specific protein kinase activityin vitro4–6and interacts with cellular membranes7, but the biochemical basis of its ability to transform remains unclear. Although there is some correlation between the transforming activity of different polyoma virus mutants and their ability to accept phosphate on tyrosine in middle T in thein vitrokinase reaction4, the abundance of phos-photyrosine in protein is not elevated in polyoma virus-transformed cells8and no cellular substrates for the putative kinase have been identified. It is also not yet known whether the tyrosine kinase of middle T is an intrinsic activity of the protein itself or the property of an associated enzyme. The experiments described here indicate that a fraction of middle T forms a stable complex with pp60c-src, the product of a cellular oncogene9, and lead us to propose that the middle T associated kinase at least in part is a property of pp60c-srcrather than middle T itself.