Valentinis B, Morrione A, Taylor S J, Baserga R
Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Mol Cell Biol. 1997 Jul;17(7):3744-54. doi: 10.1128/MCB.17.7.3744.
R- cells, a line of mouse embryo fibroblasts with a targeted disruption of the insulin-like growth factor I (IGF-I) receptor genes, are refractory to transformation by several viral and cellular oncogenes. Using colony formation in soft agar as a measure of full transformation, we report here that R- cells can be transformed by v-src, although they still cannot be transformed by the activated c-src527 (mutation at tyrosine 527 to phenylalanine), which readily transforms mouse embryo cells with a wild-type number of IGF-I receptors (W cells). Although v-src is a more potent inducer of tyrosine phosphorylation than c-src527, the extent of phosphorylation of either insulin receptor substrate 1 or Shc, two of the major substrates of the IGF-I receptor, does not seem sufficiently different to explain the qualitative difference in soft agar growth. v-src, however, is considerably more efficient than c-src527 in its ability to tyrosyl phosphorylate, in R- cells, the focal adhesion kinase, Stat1, and p130cas. These results indicate that v-src, but not c-src527, can bypass the requirement for a functional IGF-I receptor in the full transformation of mouse embryo fibroblasts and suggest that qualitative and quantitative differences between the two oncogenes can be used to identify some of the signals relevant to the mechanism(s) of transformation.
R-细胞是一种小鼠胚胎成纤维细胞系，其胰岛素样生长因子I（IGF-I）受体基因被靶向破坏，对几种病毒和细胞癌基因的转化具有抗性。我们以软琼脂中的集落形成作为完全转化的指标，在此报告R-细胞可被v-src转化，尽管它们仍不能被活化的c-src527（酪氨酸527突变为苯丙氨酸）转化，而c-src527能轻易地将具有野生型数量IGF-I受体的小鼠胚胎细胞（W细胞）转化。尽管v-src比c-src527是更强的酪氨酸磷酸化诱导剂，但胰岛素受体底物1或Shc（IGF-I受体的两个主要底物）的磷酸化程度似乎没有足够差异来解释软琼脂生长中的质的差异。然而，在R-细胞中，v-src使粘着斑激酶、Stat1和p130cas酪氨酸磷酸化的能力比c-src527高效得多。这些结果表明，在小鼠胚胎成纤维细胞的完全转化中，v-src而非c-src527可以绕过对功能性IGF-I受体的需求，并表明这两种癌基因之间的质和量的差异可用于识别一些与转化机制相关的信号。
