Bais C, Santomasso B, Coso O, Arvanitakis L, Geras Raaka E, Gutkind JS, Asch AS, Cesarman E, Gershengorn MC, Mesri EA; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 5th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 5th 1998 Chic Ill. 1998 Feb 1-5; 5th: 178 (abstract no. 527).
Cornell University Medical College, New York, NY.
Kaposi's sarcoma-associated herpesvirus/Human Herpesvirus 8 (KSHV/HHV 8) is a virus implicated in the pathogenesis of malignant lymphoma and Kaposi's sarcoma (KS). KSHV encodes a constitutively signaling G-protein coupled receptor (GPCR) that activates a phosphoinositide-specific phospholipase-C. We found that in NIH 3T3 cells, signaling by KSHV-GPCR leads to cell transformation and tumorigenicity in nude mice, and is sufficient to induce an angiogenic response characterized by Vascular Endothelial Growth Factor-mediated endothelial cell mitogenicity and microtubule formation. Co-expression of KSHV-GPCR with tagged MAPKs in HEK293T cells leads to activation of JUNK/SAPK and p38 MAPK but not of ERK-2/MAPK, indicating that KSHV-GPCR can recruit protein kinase cascades that are characteristic of signaling by inflammatory cytokines, which are known to activate angiogenesis and proliferation of KS and B-cells. We conclude that KSHV-GPCR is a viral oncogene that exploits cell signaling pathways leading to angiogenesis and transformation. The fact that KSHV-GPCR is expressed in KSHV associated malignancies points to a causal role for KSHV in lymphomagenesis and KS pathogenesis.
Publication Types:
Keywords:
- Animals
- G protein-coupled receptor, Human herpesvirus 8
- Genes, Viral
- Herpesvirus 8, Human
- Humans
- MAP3K8 protein, human
- Mice
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinases
- Proto-Oncogene Proteins
- Receptors, Chemokine
- Receptors, G-Protein-Coupled
- Sarcoma, Kaposi
- Signal Transduction
- genetics
- p38 Mitogen-Activated Protein Kinases
Other ID:
UI: 102236111
From Meeting Abstracts