MECHANISMS OF R RAS CELL ADHESION SIGNALING

描述：（改编自研究者摘要）本申请 旨在研究细胞粘附改变的机制， ras相关的GTB结合蛋白R-ras诱导。 他们希望能找出 导致整联蛋白活化的新组分和随后的研究 因为它们在肿瘤中的失调。 具体目标如下：1） 以确定R-ras中哪些残基编码细胞粘附中的序列。 将使用R-ras和H-ras之间的嵌合突变体。 2)的作用 R-ras介导细胞粘附功能的各种效应物将被 描绘的。 一组具有不同能力的R-ras功能突变体， 检测诱导细胞粘附与Ras相互作用的能力 效应器 3)具体目标#3将评估R-ras在调节细胞凋亡中的作用。 细胞粘附通过改变下游事件介导的ras，如 ras/raf MAP激酶通路。 在这个特定的目标中， R-ras和ras之间的交叉顶部将在以下方面进行探索 在细胞分裂期间调节细胞粘附。 总之，这一建议 讨论了有关机制的一些重要和及时的问题， ras相关的G蛋白通过其赋予信号特异性， 重要的生物功能，如细胞粘附。

DESCRIPTION: (adapted from the investigator's abstract) This application aims to study the mechanisms involved in alterations in cell adhesion induced by ras related GTB binding protein R-ras. They hope to identify novel components leading to integrin activation and the subsequent search for their de-regulation in tumors. The specific aims are the following: 1) to identify which residues within R-ras code for sequences in cell adhesion. Chimeric mutants between R-ras and H-ras will be used. 2) The role of various effectors of R-ras mediating cell adhesion functions will be delineated. A panel of R-ras functional mutants with varying abilities to induce cell adhesion will be examined for their ability to interact with ras effectors. 3) Specific aim #3 will assess the role of R-ras in modulating cell adhesion by altering the downstream events mediated by ras such as the ras/raf MAP kinase pathway. In this specific aim the biologic consequences of crossed top between R-ras and ras will be explored with respect to regulating cell adhesion during cell division. In summary this proposal addresses some of the important and timely issues concerning the mechanisms by which ras related G proteins confer signaling specificity in controlling vital biologic functions such as cell adhesion.