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

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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.