Application of high throughput technology to the study of the human kinome

几十年来，细胞接收、传递和响应环境提供给它的信息的精确机制一直是生物学研究的焦点。所有的刺激都利用信号级联，利用蛋白激酶将信息从环境传递到细胞中。我研究的长期目标是建立一个具有国际竞争力的项目，旨在在基因组水平上阐明控制细胞信息传递的信号通路，以期了解这些事件发生的功能生物学背景（细胞生长、分裂、运动、死亡）。这一建议的新颖之处在于系统的、基于质谱的方法来确定人类蛋白激酶的一致磷酸化位点，目的是建立一个哺乳动物激酶的全面图谱：底物特异性。因此，这些结果可能会引起广泛的纯生物学家和应用生物学家的普遍兴趣。

The precise mechanisms whereby a cell receives, transmits and responds to information presented to it by its environment have been the focus of intense research in biology for several decades. All stimuli utilize signaling cascades that utilize protein kinases to transmit information from the environment into the cell. The long term objective of my research is to establish an internationally competitive program designed to elucidate on a genomic level the signaling pathways that control cellular information transfer, with a view to understanding the functional biological context (cell growth, division, movement, death) in which these events take place. The novelty of this proposal is the systematic, mass spectrometry based approach to identify consensus phosphorylation sites for human protein kinases with the goal of establishing a comprehensive map of mammalian kinase:substrate specificity. The results are therefore likely to be both of general interest to a wide range of both pure and applied biologists.