RUI: G Protein-Coupled Receptor Kinase 2 (GRK2): Mechanism of Activation

细胞之间的信号需要调节身体的高级功能，如心率、葡萄糖代谢和感觉。激素和神经递质等信号分子与靶细胞上的受体相互作用，启动一系列事件，最终导致生理效应。其中一种受体称为G蛋白偶联受体(GPCR)，它传递许多细胞间信息，代表人类基因组编码的一大类蛋白质。虽然激素和神经递质启动了信号级联，但细胞内的蛋白质需要终止，从而调节受体信号。这项研究的重点是一种名为GPCRK(GRK2)的调节蛋白，它在与激活的受体相互作用以终止信号方面发挥关键作用。这项研究的一个目标是绘制GRK2与其调节的受体之间的结合界面。希望这些研究将阐明这类新蛋白被激活的机制，并最终导致GRK2抑制剂的合理设计。该项目将在一个以本科生为主的机构进行，并将使更多的未来科学家接触结构、分子和细胞技术。与研究密集型大学的研究人员广泛合作，将确保最新技术的注入，这将反映在遗传学、细胞生物学、分子生物学和生物化学课程中。首席调查员将保持吸引本科生参与研究和培养职业科学家的良好记录，特别是那些来自代表性不足群体的本科生。为了进一步扩大代表不足的人群的参与，国际学生联合会将继续与锡耶纳学院的高等教育机会计划(HEOP)合作，招募HEOP学生参与拟议的研究。HEOP是纽约州一所针对经济和学业困难学生的计划。

Signaling between cells is required to regulate higher order functions in the body such as heart rate, glucose metabolism, and sensory perception. Signaling molecules such as hormones and neurotransmitters interact with receptors on target cells and initiate a cascade of events that culminates in a physiological effect. One type of receptor, termed G protein-coupled receptor (GPCR), transduces many intercellular messages and represents a large class of proteins encoded by the human genome. While hormones and neurotransmitters initiate signaling cascades, intracellular proteins are required to terminate and thereby regulate receptor signaling. The focus of this study is a regulatory protein called GPCR kinase (GRK2) that plays a crucial role in interacting with activated receptors to terminate the signal. One goal of this investigation is to map the binding interface between GRK2 and the receptors it regulates. It is hoped that these studies will illuminate the mechanism by which this novel class of proteins is activated and ultimately lead to the rational design of GRK2 inhibitors. This project will be carried out at a predominantly undergraduate institution and will expose a wider population of future scientists to structural, molecular and cellular techniques. Extensive collaborations with investigators at research-intensive universities will ensure the infusion of the latest technology and this will be reflected in the genetics, cell biology, molecular biology and biochemistry curricula. The principle investigator will maintain strong record of engaging undergraduates, especially those from under-represented groups, in research and producing career scientists. To further broaden the participation of under-represented populations, the PI will continue to work with Siena College's Higher Education Opportunity Program (HEOP), a New York State college program for economically and academically disadvantaged students, to recruit HEOP students to participate in the proposed research.