ANALYSIS OF EUKARYOTIC PROTEIN KINASES AND PHOSPHO-REGULATORY SYSTEMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 人类基因组编码了500多个蛋白激酶。这些激酶催化将ATP的γ-磷酸转移到其目标蛋白上的特定羟基上。这种磷酸化事件可以诱导构象变化或促进大分子组装的形成。突变或病毒颠覆机制引起的蛋白激酶功能异常会导致细胞功能障碍，这些疾病是许多人类疾病的基础。通过使用小分子疗法来对抗蛋白激酶功能异常的能力已经证实了蛋白激酶是一个可用药的靶点。蛋白激酶作为细胞生物学调节剂的普遍性，源于一种结构的可塑性，这种结构允许催化开关和底物识别机制的多样化。到目前为止，只有一小部分真核蛋白激酶被结构表征。在我的实验室里，我们正在寻求揭示新型催化开关、底物识别和下游磷酸调节机制的结构基础。我们的长期目标是利用我们所学到的蛋白激酶和磷酸调节系统来开发治疗疾病的药物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The human genome encodes just over 500 protein kinases. These kinases catalyze the transfer of the gamma phosphate of ATP to a specific hydoxyl group onto their target protein. This phosphorylation event can induce conformational changes or promote the formation of macromolecular assemblies. Aberrant protein kinase function arising from mutation or viral subversion mechanisms gives rise to cellular dysfunctions that underlie numerous human diseases. The ability to counteract aberrant protein kinase function through the use of small molecule therapeutics has validated the protein kinase as a drugable target. The pervasiveness of protein kinases as regulators of cellular biology, stems from a plasticity of structure that allows for the diversification of catalytic switching and substrate recognition mechanisms. To date only a small fraction of eukaryotic protein kinases have been structurally characterized. In my lab, we are seeking to uncover the structural basis for novel catalytic switching, substrate recognition and down-stream phospho-regulatory mechanisms. Our long-term goal is to make use of what we learn about protein kinases and phospho-regulatory systems to develop drugs to treat disease.