Grant: Discovery Grants Program - Individual

Cells communicate with one another and recognize changes in their environment through the use of receptorswhich detect specific chemical or physical signals. The majority of receptors produce their effects byactivating a second protein inside the cell known as a G protein. The activated G protein then is able to produceeffects on other cellular processes, thus allowing the cell to respond in an appropriate way to the originalexternal signal. In addition, there are auxiliary proteins inside the cell that regulate the G protein effectstriggered by the receptors. For example, to counter the activating effects of receptors there are proteins whosejob it is to either turn G proteins off (RGS proteins) or prevent G proteins from being turned on (GoLocoproteins). Intriguingly, several regulatory proteins have been discovered that contain multiple domains that canact on G proteins in different ways. In some cases, these functions appear to be either redundant or at oddswith one another, at least based on what we know about their biochemistry. For example, the protein RGS14simultaneously has the potential to both prevent G protein activation (via its GoLoco motif) and turn offactivated G proteins (via its RGS domain). There is another GoLoco-based protein known as G18 that isknown to prevent G protein activation, but our laboratory has found that a previously uncharacterized part ofthis protein molecule can do the opposite, that is, it promotes G protein activation. The existence of thesecomplex 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-interactingdomains of RGS14 and G18 work together to control receptor signals. This will increase our understanding ofhow cells communicate with each other and respond to changes in their environment.