Whitman M, Kaplan D, Cantley L, Roberts T M, Schaffhausen B
Fed Proc. 1986 Oct;45(11):2647-52.
We have used the DNA tumor virus polyoma as a model system to examine whether the phosphatidylinositol (PI) turnover pathway is a critical target for transforming gene products. Polyoma-infected cells show elevated levels of polyphosphoinositides and polyphosphoinositols, and a PI kinase activity is associated with middle T antigen, a transforming gene product of polyoma virus. In anti-T immunoprecipitates from polyoma-infected or -transformed cells, comparisons of wild-type and polyoma mutants defective for transformation show a strong correlation between middle T-associated PI kinase activity and transforming ability. Middle T has previously been found to associate at the plasma membrane with pp60 c-src and to activate it as a tyrosine kinase. c-src itself does not appear to phosphorylate PI; however, the middle T/pp60 c-src tyrosine kinase activity may be important for activation of PI kinase. Ammonium orthovanadate, a tyrosine phosphatase inhibitor, elevates the middle T/pp60 c-src-associated PI kinase activity. We propose that middle T/pp60 c-src activates a PI kinase and modulates PI turnover in vivo by tyrosine phosphorylation.
我们已将DNA肿瘤病毒多瘤病毒用作模型系统，以研究磷脂酰肌醇（PI）代谢途径是否是转化基因产物的关键靶点。多瘤病毒感染的细胞显示多磷酸肌醇和多磷酸肌醇水平升高，并且PI激酶活性与中T抗原相关，中T抗原是多瘤病毒的一种转化基因产物。在来自多瘤病毒感染或转化细胞的抗T免疫沉淀物中，对野生型和转化缺陷的多瘤病毒突变体的比较显示，中T相关的PI激酶活性与转化能力之间存在很强的相关性。先前已发现中T在质膜上与pp60 c-src结合，并将其激活为酪氨酸激酶。c-src本身似乎不会使PI磷酸化；然而，中T/pp60 c-src酪氨酸激酶活性可能对PI激酶的激活很重要。酪氨酸磷酸酶抑制剂原钒酸铵可提高中T/pp60 c-src相关的PI激酶活性。我们提出，中T/pp60 c-src激活PI激酶并通过酪氨酸磷酸化在体内调节PI代谢。
