N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias
Copyright policy )N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias
Significance G-protein-coupled receptors (GPCRs) are the largest class of mammalian signaling receptors and mediate vast physiological responses. The capacity to modulate GPCR signaling therapeutically is important for treatment of various diseases, and discovering new aspects of receptor signaling is critical for drug development. Protease-activated receptor-1 (PAR1) is GPCR for thrombin. Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell. How a single GPCR can couple to multiple G-protein subtypes concurrently has remained an enigma. We demonstrate that N-linked glycosylation of PAR1 regulates G-protein coupling specificity and differentially controls cellular responses. Thus, the status of GPCR glycosylation is a critical determinant for specifying coupling to distinct G-protein subtypes.
- University of California System United States
- Beckman Research Institute United States
- UNIVERSITY OF CALIFORNIA SAN DIEGO
- University of California, San Francisco United States
- UNIVERSITY OF CALIFORNIA, SAN DIEGO
570, Glycosylation, Knockout, Immunoblotting, 610, PAR-1, GTP-Binding Protein alpha Subunits, G12-G13, Mice, GPCR, endothelial, Chlorocebus aethiops, 2.1 Biological and endogenous factors, Animals, Humans, Receptor, PAR-1, Gq-G11, Mice, Knockout, Binding Sites, arrestin, Thrombin, RhoA, Biological Sciences, Fibroblasts, thrombin, GTP-Binding Protein alpha Subunits, Hela Cells, COS Cells, Mutation, GTP-Binding Protein alpha Subunits, Gq-G11, RNA Interference, Biochemistry and Cell Biology, G12-G13, rhoA GTP-Binding Protein, Algorithms, Receptor, HeLa Cells, Protein Binding, Signal Transduction, Thymidine
570, Glycosylation, Knockout, Immunoblotting, 610, PAR-1, GTP-Binding Protein alpha Subunits, G12-G13, Mice, GPCR, endothelial, Chlorocebus aethiops, 2.1 Biological and endogenous factors, Animals, Humans, Receptor, PAR-1, Gq-G11, Mice, Knockout, Binding Sites, arrestin, Thrombin, RhoA, Biological Sciences, Fibroblasts, thrombin, GTP-Binding Protein alpha Subunits, Hela Cells, COS Cells, Mutation, GTP-Binding Protein alpha Subunits, Gq-G11, RNA Interference, Biochemistry and Cell Biology, G12-G13, rhoA GTP-Binding Protein, Algorithms, Receptor, HeLa Cells, Protein Binding, Signal Transduction, Thymidine
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