RECONSTITUTION OF GROWTH FACTOR RECEPTOR TYROSINE KINASE

描述(改编自《调查员摘要》)：此应用程序是 RO1的更新以了解EGF受体的作用机制 家庭成员被激活并发出信号。受体家族包括 EGF受体本身、Neu、ErbB3和ErbB4。这一点在 与特定受体结合的配基诱导或 稳定同二聚体或异二聚体的形成。后者的属性为 特别有趣，但不是特别出名。首字母 该提案的重点是在ErbB3和ErbB3之间建立的复合体 Neu和EGF受体及Neu。第一个目标涉及的是 激活，特别是ErbB3，它不是一种有效的酪氨酸 激酶，促进Neu与Hereguline结合后的激活，以及Neu是否 完全由EGF受体激活。这两个问题的答案都是 通过重组纯化的正常或突变蛋白在 磷脂小泡。第二个目标是解决近端信号传递问题 分子。一种假设是Neu对ErbB3的酪氨酸磷酸化 解释了ErbB3与P85的结合。同样需要研究的是这种机制 通过它，EGF受体实现Cb1原癌基因的磷酸化。 第三个目标是更好地了解EGF受体所使用的途径。 更远的下游家庭。激活的可能性 应激激活的MAP激酶将被检测，因为存在一些证据 对于CDC42的激活，以及一个新的GTP结合蛋白的鉴定 还将探索由EGF和Hereglin激活的机制。GTP绑定 蛋白质是核的，与RCC1结合，并被紫外线和 增长因素。

DESCRIPTION (Adapted from the Investigator's Abstract): This application is a renewal of an RO1 to understand the mechanisms by which EGF receptor family members are activated and signal. The family of receptors includes the EGF receptor itself, Neu, ErbB3 and ErbB4. It is noted in the application that ligand binding to a particular receptor induces or stabilizes homo- or heterodimer formation. The properties of the latter are especially interesting but not particularly well known. The initial emphasis of the proposal is on complexes established between the ErbB3 and Neu and the EGF receptor and Neu. The first aim deals with mechanisms of activation, and specifically how ErbB3, which is not an effective tyrosine kinase, promotes activation of Neu upon binding heregulin, and whether Neu is activated at all by the EGF receptor. The answers to both will be achieved by reconstitution of purified normal or mutant proteins in phospholipid vesicles. The second aim addresses proximal signaling molecules. One hypothesis is that tyrosine phosphorylation of ErbB3 by Neu accounts for binding of ErbB3 to p85. Also to be examined is the mechanism by which the EGF receptor achieves phosphorylation of the Cbl protooncogene. The third aim is to understand better pathways employed by the EGF receptor family further downstream. The potential for activation of the stress-activated MAP kinases will be examined, since some evidence exists for Cdc42 activation, and the identity of a novel GTP-binding protein activated by EGF and heregulin will also be explored. The GTP-binding protein is nuclear, binds RCC1, and is activated by UV light as well as growth factors.