SILAC analysis of compartmentalised Ras signalling

区室 Ras 信号传导的 SILAC 分析

• 批准号: BB/G018162/1
• 负责人: Ian Prior
• 金额: $ 35.95万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG018162%2F1
• 关键词: SILAC; analysis; compartmentalised; Ras; signalling

We are interested in Ras proteins that sit near the top of many cell signalling pathways and control key cellular functions such as proliferation, migration and cell death. Cells contain three almost identical versions (isoforms) that differ only in their preferred locations within the cell. These overlapping localisations are believed to underlie the biological differences known to exist between the isoforms. This model suggests that by operating from different platforms within the cell, Ras isoforms will come into contact with distinct pools of activators and downstream signalling proteins. We plan to test this model by targetting Ras to each of the different organelles where it is known to reside and compare the signals that are produced. We will use new technology that enables the responses of networks containing thousands of proteins to be precisely analysed. Our datasets will be mined to reveal likely relationships between signalling from each compartment and functional outputs that will be confirmed using cell-based assays. Together these data will provide a comprehensive picture of compartment-specific signalling.

我们对位于许多细胞信号通路顶部附近并控制关键细胞功能（如增殖、迁移和细胞死亡）的 Ras 蛋白感兴趣。细胞包含三个几乎相同的版本（异构体），仅在细胞内的首选位置不同。这些重叠的定位被认为是亚型之间已知存在的生物学差异的基础。该模型表明，通过在细胞内的不同平台上操作，Ras 亚型将与不同的激活剂和下游信号蛋白池接触。我们计划通过将 Ras 定位到已知其驻留的每个不同细胞器并比较产生的信号来测试该模型。我们将使用新技术来精确分析包含数千种蛋白质的网络的反应。我们将挖掘我们的数据集，以揭示每个区室的信号传导与功能输出之间的可能关系，这些关系将使用基于细胞的测定进行确认。这些数据将共同提供隔间特定信号的全面描述。

项目成果

Comparative proteomic analysis of compartmentalised Ras signalling.

• DOI: 10.1038/srep17307
• 发表时间: 2015-12-01
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Hernandez-Valladares M;Prior IA
• 通讯作者: Prior IA

A comprehensive survey of Ras mutations in cancer.

• DOI: 10.1158/0008-5472.can-11-2612
• 发表时间: 2012-05-15
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Prior IA;Lewis PD;Mattos C
• 通讯作者: Mattos C

Ras trafficking, localization and compartmentalized signalling.

• DOI: 10.1016/j.semcdb.2011.09.002
• 发表时间: 2012-04
• 期刊: SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
• 影响因子: 7.3
• 作者: Prior, Ian A.;Hancock, John F.
• 通讯作者: Hancock, John F.