ROLE IN SHC IN NORMAL AND MALIGNANT SIGNAL TRANSDUCTION

描述：（改编自研究者摘要）Shc基因 编码三种广泛表达的蛋白质， 通过多种蛋白酪氨酸激酶进行信号转导。 两 细胞质和受体蛋白酪氨酸激酶可致癌 Shc在表达酪氨酸磷酸化的细胞中被激活， 致癌激活蛋白酪氨酸激酶。 Shc蛋白缺乏 催化活性，并被认为是作为一个支架， 蛋白质相互作用 两个磷酸酪氨酸结合模块， 几个酪氨酸磷酸化位点使Shc能够介导几个 蛋白质间的相互作用。 Shc变成酪氨酸 在与活化的生长因子受体结合后磷酸化。 酪氨酸磷酸化的Shc与Grb 2-Sos复合物结合， 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。 委员会还 尚不清楚Shc是否独立于Ras发挥功能。其长期 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 图1显示了Shc缺陷细胞中Shc突变体集合的信号传导能力。 此外，他们还将确定Shc和Hc之间信号传导的差异。 和Grb 2，他们提出， 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.