Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor signals through multiple pathways in endothelial cells.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) encodes a chemokine-like G protein-coupled receptor (KSHV-GPCR) that is implicated in the pathogenesis of Kaposi's sarcoma (KS). Since endothelial cells appear to be targets for the virus, we developed an in vitro mouse lung endothelial cell model in which KSHV-GPCR is stably expressed and KSHV-GPCR signaling was studied. In mouse lung endothelial cells: 1) KSHV-GPCR does not exhibit basal signaling through the phosphoinositide-specific phospholipase C pathway but inositol phosphate production is stimulated by growth-related oncogene alpha (Gro-alpha) via a pertussis toxin (PTX)-insensitive pathway; 2) KSHV-GPCR signals basally through a PTX-sensitive pathway leading to a lowering of intracellular cAMP level that can be lowered further by Gro alpha and increased by interferon gamma-inducible protein 10; 3) KSHV-GPCR stimulates phosphatidylinositol 3-kinase via a PTX-insensitive mechanism; and 4) KSHV-GPCR activates nuclear factor-kappa B (NF-kappa B) by a PTX-sensitive G beta gamma subunit-mediated pathway. These data show that KSHV-GPCR couples to at least two G proteins and initiates signaling via at least three cascades in endothelial cells thereby increasing the complexity of regulation of endothelial cell function by KSHV-GPCR that may occur during viral infection.

• Authors: J P Couty, E Geras-Raaka, B B Weksler, M C Gershengorn
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 36 Pg. 33805-11 (Sep 07 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11448967 (Publication Type: Journal Article)

Chemical References

• G protein-coupled receptor, Human herpesvirus 8
• NF-kappa B
• Receptors, Chemokine
• Virulence Factors, Bordetella
• Colforsin
• Cyclic AMP
• Luciferases
• Pertussis Toxin
• Phosphatidylinositol 3-Kinases
• Type C Phospholipases
• Adenylyl Cyclases

Topics

• Adenylyl Cyclases (metabolism)
• Animals
• Animals, Newborn
• Binding, Competitive
• Cell Survival
• Colforsin (metabolism)
• Cyclic AMP (metabolism)
• Dose-Response Relationship, Drug
• Endothelium (metabolism)
• Enzyme Activation
• Fibroblasts (metabolism)
• Luciferases (metabolism)
• Lung (metabolism)
• Mice
• NF-kappa B (metabolism)
• Pertussis Toxin
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein Binding
• Receptors, Chemokine (metabolism)
• Signal Transduction
• Time Factors
• Transfection
• Type C Phospholipases (metabolism)
• Virulence Factors, Bordetella (pharmacology)