Transformation and tumorigenic properties of a mutant polyomavirus containing a middle T antigen defective in Shc binding.
Transformation and tumorigenic properties of a mutant polyomavirus containing a middle T antigen defective in Shc binding.
复制标题
含有 Shc 结合缺陷的中间 T 抗原的突变多瘤病毒的转化和致瘤特性。
DOI：
10.1128/jvi.71.9.6279-6286.1997
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发表时间：
1997
影响因子：
5.4
通讯作者：
Freund,R
中科院分区：
文献类型：
--
作者：
Yi,X;Peterson,J;Freund,R
多瘤病毒中T抗原在几个酪氨酸残基上磷酸化，这些酪氨酸残基充当细胞蛋白的结合位点，包括磷脂酰肌醇3-激酶、Shc和磷脂酶C-γ。在这份报告中，我们描述了一种多瘤病毒的转化特性和肿瘤诱导能力，该病毒在中间T抗原中含有一个单位点突变，将氨基酸位置250处的酪氨酸残基改变为丝氨酸。这种突变破坏了中间T与转化蛋白Shc的结合。突变病毒转化能力弱，诱导的病灶比野生型的病灶小且形态不同。尽管病毒在接近100%的接种小鼠中诱导肿瘤，但与野生型病毒相比，肿瘤谱及其形态发生了改变。突变病毒诱导肾脏和胸腺肿瘤的发生率降低。诱导的乳腺和胸腺肿瘤在组织学上与野生型多瘤病毒诱导的肿瘤不同。这些结果表明，由中间T-Shc关联解除调节的信号转导途径对于培养物中细胞的完全转化和小鼠-多瘤病毒系统中某些靶组织中的肿瘤诱导是重要的。
Polyomavirus middle T antigen is phosphorylated on several tyrosine residues which act as binding sites for cellular proteins, including phosphatidylinositol 3-kinase, Shc, and phospholipase C-gamma. In this report we describe the transforming properties and tumor-inducing ability of a polyomavirus that contains a single-site mutation in middle T antigen which changes a tyrosine residue at amino acid position 250 to serine. This mutation disrupts the association of middle T with the transforming protein Shc. The mutant virus is weakly transforming, inducing foci which are smaller and of different morphology than those of the wild type. Although the virus induced tumors in close to 100% of inoculated mice, the spectrum of tumors and their morphology were altered compared to those of wild-type virus. The mutant virus induced a reduced frequency of kidney and thymic tumors. Both the mammary gland and the thymic tumors that were induced were histologically distinct from those induced by wild-type polyomavirus. These results demonstrate that the signal transduction pathway that is deregulated by the middle T-Shc association is important for full transformation of cells in culture and for tumor induction in some target tissues in the mouse-polyomavirus system.