Integration of signals by proteins that have multiple G protein-interacting domains

点击翻译按钮获取中文摘要

Cells communicate with one another and recognize changes in their environment through the use of receptors which detect specific chemical or physical signals. The majority of receptors produce their effects by activating a second protein inside the cell known as a G protein. The activated G protein then is able to produce effects on other cellular processes, thus allowing the cell to respond in an appropriate way to the original external signal. In addition, there are auxiliary proteins inside the cell that regulate the G protein effects triggered by the receptors. For example, to counter the activating effects of receptors there are proteins whose job it is to either turn G proteins off (RGS proteins) or prevent G proteins from being turned on (GoLoco proteins). Intriguingly, several regulatory proteins have been discovered that contain multiple domains that can act on G proteins in different ways. In some cases, these functions appear to be either redundant or at odds with one another, at least based on what we know about their biochemistry. For example, the protein RGS14 simultaneously has the potential to both prevent G protein activation (via its GoLoco motif) and turn off activated G proteins (via its RGS domain). There is another GoLoco-based protein known as G18 that is known to prevent G protein activation, but our laboratory has found that a previously uncharacterized part of this protein molecule can do the opposite, that is, it promotes G protein activation. The existence of these complex proteins strongly suggests that there are undiscovered ways in which cells deal with receptor signals. The proposed studies will investigate how the combined functions of the multiple G protein-interacting domains of RGS14 and G18 work together to control receptor signals. This will increase our understanding of how cells communicate with each other and respond to changes in their environment.