CELL TRANSFORMATION BY INSULIN AND IGFI RECEPTORS

这项拟议研究的目标是利用胰岛素受体(IR)和 含胰岛素样生长因子I受体(IGFR)CDNA 逆转录病毒，阐明细胞转化的生化基础。 IR和IGFR是受体PTK家族中的两个成员，它们在 在细胞代谢活动和有丝分裂中的重要调节作用。 我们已经证明了它的转化和致癌潜力 IR和IGFR可以通过将它们的部分CDNA序列放置在 逆转录病毒。 我们在这项研究中的具体目标是1)识别结构 负责转化和致癌激活的基础 人胰岛素抵抗和胰岛素样生长因子受体的潜能；2)哺乳动物细胞系的建立 IR和IGFR逆转录病毒突变株IR和IGFR的转化 蛋白质及其差异转化潜能的相关性； 以及4)识别潜在的细胞底物 突变的IR和IGFR蛋白对细胞的转化。 希望这项研究将进一步加深我们对 这些受体PTK基因转化细胞的机制。

The goals of this proposed study is to employ insulin receptor (IR) and insulin-like growth factor I receptor (IGFR) CDNA-containing retroviruses to elucidate the biochemical basis of cell transformation. IR and IGFR are two members of the receptor PTK family which play an important regulatory role in cellular metabolic activities and mitosis. We have demonstrated that the transforming and tumorigenic potential of IR and IGFR can be manifested by placing part of their CDNA sequences in retroviruses. Our specific aims in this study are 1) identification of the structural basis responsible for activation of the transforming and tumorigenic potential of human IR and IGFR; 2) establishment of mammalian cell lines transformed by IR and IGFR-containing retroviruses mutant IR and IGFR proteins and correlation with their differential transforming potential; and 4) identification of potential cellular substrates important for cell transformation by mutant IR and IGFR proteins. It is hoped that this study will further our understanding of the mechanism of cell transformation by those receptor PTK genes.