The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. Academic Article uri icon

Overview

abstract

  • The Kaposi's sarcoma-associated herpesvirus (KSHV), the infectious causative agent of Kaposi's sarcoma (KS), encodes a G protein-coupled receptor (vGPCR) implicated in the initiation of KS. Here we demonstrate that Kaposi's sarcomagenesis involves stimulation of tuberin (TSC2) phosphorylation by vGPCR, promoting the activation of mTOR through both direct and paracrine mechanisms. Pharmacologic inhibition of mTOR with rapamycin prevented vGPCR sarcomagenesis, while overactivation of this pathway was sufficient to render endothelial cells oncogenic. Moreover, mice haploinsufficient for TSC2 are predisposed to vascular sarcomas remarkably similar to KS. Collectively, these results implicate mTOR in KS initiation and suggest that the sarcomagenic potential of KSHV may be a direct consequence of the profound sensitivity of endothelial cells to vGPCR dysregulation of the TSC2/mTOR pathway.

publication date

  • August 1, 2006

Research

keywords

  • Cell Transformation, Neoplastic
  • Endothelial Cells
  • Herpesvirus 8, Human
  • Protein Kinases
  • Receptors, Chemokine
  • Tumor Suppressor Proteins
  • Viral Proteins

Identity

Scopus Document Identifier

  • 33746832011

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2006.05.026

PubMed ID

  • 16904612

Additional Document Info

volume

  • 10

issue

  • 2