THROMBIN RECEPTOR-G PROTEIN SIGNALING MECHANISMS

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DESCRIPTION Thrombin is generated in response to vascular injury, and is involved in thrombotic, inflammatory, and proliferative processes. Thrombin cleaves at least three heterotrimeric G protein-coupled peptide receptors (GPCRs) known as protease-activated receptors (PAR. PAR1 is the prototypical thrombin receptor, and is found on platelets, vascular smooth muscle cells, endothelial cells, and many other cell types. PAR3 and PAR4 are involved in platelet activation in mice and humans. The goal of this research is to gain understanding of the interactions of G proteins with the PARs expressed in yeast. Expression of these proteins in yeast yields a specific G protein-receptor pair in isolation from other mammalian G proteins and receptors. This eliminates concerns of data being contaminate by the plethora of different G proteins present in mammalian cells. In addition, coupling these receptors to the yeast mating pathway will allow efficient analysis of mutations that alter ligand receptor and G protein receptor interactions with cannot be done by conventional mammalian cell methods. The yeast two-hybrid system will be used to examine interactions of the intracellular loops of the thrombin receptor with G proteins, and potentially to discover other types of proteins interacting with receptor loops.