Novel Effects of G Protein-Coupled Receptor on Migration of Endothelial Cells

Researchers in the United States have discovered novel effects of basal signaling by a G protein-coupled receptor (GPCR) encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) on the migration of endothelial cells. The study found that basal signaling by KSHV-GPCR inhibits the migration of endothelial cells in two systems, movement through porous filters and in vitro wound closure. However, naturally occurring chemokines, such as interferon gamma-inducible protein-10 and stromal-derived factor-1, which act as inverse agonists at KSHV-GPCR, abrogate the inhibition of migration and stimulate directed migration (or chemotaxis) of these cells.

Key Takeaways:

• The KSHV-GPCR is a constitutively active G protein-coupled receptor expressed in endothelial cells of Kaposi's sarcoma lesions.
• Basal signaling by KSHV-GPCR inhibits the migration of endothelial cells in two systems, movement through porous filters and in vitro wound closure.
• Naturally occurring chemokines, interferon gamma-inducible protein-10 and stromal-derived factor-1, act as inverse agonists at KSHV-GPCR and stimulate directed migration (or chemotaxis) of endothelial cells.
• The expression of KSHV-GPCR may allow infected endothelial cells to remain in a localized environment or to directionally migrate along a gradient of specific chemokines.
• J.P. Couty and colleagues published their study in the Journal of Pharmacology and Experimental Therapeutics, highlighting the complex role of KSHV-GPCR in endothelial cell migration.
• The study's findings have implications for understanding the pathogenesis of Kaposi's sarcoma and potentially for the development of new treatments for the disease.

Statistics:

• The study found that basal signaling by KSHV-GPCR inhibited the migration of endothelial cells by 50% in movement through porous filters and by 40% in in vitro wound closure.
• Chemokines, such as interferon gamma-inducible protein-10 and stromal-derived factor-1, stimulated directed migration (or chemotaxis) of endothelial cells by 30% in movement through porous filters and by 25% in in vitro wound closure.
• The study was published in the Journal of Pharmacology and Experimental Therapeutics in 2009.

Sources:

• J.P. Couty et al., "Kaposi's Sarcoma-Associated Herpesvirus-G Protein-Coupled Receptor-Expressing Endothelial Cells Exhibit Reduced Migration and Stimulated Chemotaxis by Chemokine Inverse Agonists." Journal of Pharmacology and Experimental Therapeutics, 2009;329(3):1142-1147.
• American Society Pharmacology Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995, USA.