Wang L H, Hanafusa H
Rockefeller University, New York, NY 10021.
Virus Res. 1988 Feb;9(2-3):159-203. doi: 10.1016/0168-1702(88)90030-5.
Twelve independent isolates of avian sarcoma viruses (ASVs) can be divided into four groups according to the transforming genes harbored in the viral genomes. The first group is represented by viruses containing the transforming sequence, src, inserted in the viral genome as an independent gene; the other three groups of viruses contain transforming genes fps, yes or ros fused to various length of the truncated structural gene gag. These transforming sequences have been obtained by avian retroviruses from chicken cellular DNA by recombination. The src-containing viruses code for an independent polypeptide, p60src; and the representative fps, yes and ros-containing ASVs code for P140/130gag-fps, P90gag-yes and P68gag-ros fusion polypeptides respectively. All of these transforming proteins are associated with the tyrosine-specific protein kinase activity capable of autophosphorylation and phosphorylating certain foreign substrates. p60src and P68gag-ros are integral cellular membrane proteins and P140/130gag-fps and P90gag-yes are only loosely associated with the plasma membrane. Cells transformed by ASVs contain many newly phosphorylated proteins and in most cases have an elevated level of total phosphotyrosine. However, no definitive correlation between phosphorylation of a particular substrate and transformation has been established except that a marked increase of the tyrosine phosphorylation of a 34,000 to 37,000 dalton protein is observed in most ASV transformed cells. The kinase activity of ASV transforming proteins appears to be essential, but not sufficient for transformation. The N-terminal domain of p60src required for myristylation and membrane binding is also crucial for transformation. By contrast, the gag portion of the FSV P130gag-fps is dispensable for in vitro transformation and removal of it has only an attenuating effect on in vivo tumorigenicity. The products of cellular src, fps and yes proto-oncogenes have been identified and shown to also have tyrosine-specific protein kinase activity. The transforming potential of c-src and c-fps has been studied and shown that certain structural changes are necessary to convert them into transforming genes. Among the cellular proto-oncogenes related to the four ASV transforming genes, c-ros most likely codes for a growth factor receptor-like molecule. It is possible that the oncogene products of ASVs act through certain membrane receptor(s) or enzyme(s), such as protein kinase C, in the process of cell transformation.
十二株独立的禽肉瘤病毒（ASV）分离株可根据病毒基因组中所含的转化基因分为四组。第一组以病毒基因组中作为独立基因插入转化序列src的病毒为代表；其他三组病毒含有与不同长度的截短结构基因gag融合的转化基因fps、yes或ros。这些转化序列是禽逆转录病毒通过重组从鸡细胞DNA中获得的。含src的病毒编码一种独立的多肽p60src；含fps、yes和ros的代表性ASV分别编码P140/130gag-fps、P90gag-yes和P68gag-ros融合多肽。所有这些转化蛋白都与能够自身磷酸化并磷酸化某些外源底物的酪氨酸特异性蛋白激酶活性相关。p60src和P68gag-ros是完整的细胞膜蛋白，而P140/130gag-fps和P90gag-yes仅与质膜松散结合。ASV转化的细胞含有许多新磷酸化的蛋白，并且在大多数情况下总磷酸酪氨酸水平升高。然而，除了在大多数ASV转化细胞中观察到34000至37000道尔顿蛋白的酪氨酸磷酸化显著增加外，特定底物的磷酸化与转化之间尚未建立明确的相关性。ASV转化蛋白的激酶活性似乎是转化所必需的，但并不充分。p60src的N末端结构域对于肉豆蔻酰化和膜结合是必需的，对于转化也至关重要。相比之下，FSV P130gag-fps的gag部分对于体外转化是可有可无的，去除它对体内致瘤性只有减弱作用。细胞src、fps和yes原癌基因的产物已被鉴定，并且也显示具有酪氨酸特异性蛋白激酶活性。已对c-src和c-fps的转化潜力进行了研究，结果表明将它们转化为转化基因需要某些结构变化。在与四个ASV转化基因相关的细胞原癌基因中，c-ros最有可能编码一种生长因子受体样分子。在细胞转化过程中，ASV癌基因产物可能通过某些膜受体或酶（如蛋白激酶C）起作用。
