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Creating Tools To Study The Signaling And Function Of The Adhesion Family Of Gpcrs, Victor M. Mirka

Electronic Thesis and Dissertation Repository

Adhesion GPCRs (aGPCRs) are difficult to study because they are activated by mechanical force. aGPCRs are autoproteolytically cleaved into N-terminal and C-terminal fragments. Mechanical force removes the N-terminal fragment revealing a tethered ligand activating the receptor. Proteinase Activated Receptors (PARs) are N-terminally cleaved by proteinases revealing a tethered ligand activating the receptor. We hypothesized the tethered ligand of aGPCRs could be revealed by replacing the N-terminal fragment with a PAR N-terminus. We fused the PAR2 N-terminus to the C-terminal fragments of four aGPCRs: CD97, EMR2, GPR56, and BAI1. PAR2-aGPCR chimeric receptors dose dependently recruited G-proteins and β-arrestins, supporting our hypothesis. …