ROLE IN SHC IN NORMAL AND MALIGNANT SIGNAL TRANSDUCTION

描述：(改编自研究人员的摘要)Shc基因 编码三种广泛表达的蛋白质，这些蛋白质有助于 多种蛋白酪氨酸激酶的信号转导。两者都有 细胞质和受体蛋白酪氨酸激酶可致癌 激活的Shc在表达的细胞中高度酪氨酸磷酸化 致癌激活的蛋白酪氨酸激酶。SHC蛋白缺失 催化活性，被认为是一种 蛋白质之间的相互作用。两个磷酸酪氨酸结合模块和 几个酪氨酸磷酸化位点使Shc能够介导几个 蛋白质与蛋白质同时相互作用。SHC变成酪氨酸 与激活的生长因子受体结合后发生磷酸化。 酪氨酸磷酸化的Shc与Grb2-SOS复合体结合，是 被认为在RAS激活中起作用。然而，Shc的精确 对RAS激活的贡献仍然知之甚少。它也保留了下来 尚不清楚Shc是否独立于RAS履行职能。他们的长期 目的是了解Shc在正常和恶性信号中的功能 转导。为了实现这一目标，他们建议将 Shc缺失细胞中一组Shc突变体的信号传递能力。 此外，他们还将确定Shc之间在信令方面的差异 和Grb2在生长因子受体激活之后，他们建议 从Src转化的成纤维细胞中纯化Shc结合蛋白。

DESCRIPTION: (adapted from the investigator's abstract) The Shc gene encodes three proteins that are widely expressed and that contribute to signal transduction by a wide variety of protein-tyrosine kinases. Both cytoplasmic and receptor protein-tyrosine kinases can become oncogenically activated and Shc is highly tyrosine-phosphorylated in cells that express oncogenically activated protein-tyrosine kinases. Shc proteins lack catalytic activity and are thought to function as a scaffold for protein-protein interactions. Two phosphotyrosine-binding modules and several tyrosine phosphorylation sites enable Shc to mediate several protein-protein interactions at the same time. Shc becomes tyrosine phosphorylated upon association with activated growth factor receptors. Tyrosine phosphorylated Shc associates with the Grb2-Sos complex and is thought to play a role in Ras activation. However, Shc's precise contribution to Ras activation remains poorly understood. It also remains unclear whether Shc performs functions independent of Ras. Their long-term goal is to understand Shc's function during normal and malignant signal transduction. To reach that goal, they propose to characterize the signaling abilities of a collection of Shc mutants in Shc-deficient cells. In addition, they will determine the differences in signaling between Shc and Grb2 following growth factor receptor activation and they propose to purify a Shc-binding protein from Src-transformed fibroblasts.