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| Item Type: | Article |
|---|---|
| Title: | Tumorigenesis induced by the HHV8-encoded chemokine receptor requires ligand modulation of high constitutive activity |
| Creators Name: | Holst, P.J., Rosenkilde, M.M., Manfra, D., Chen, S.C., Wiekowski, M.T., Holst, B., Cifire, F., Lipp, M., Schwartz, T.W. and Lira, S.A. |
| Abstract: | ORF74 (or KSHV-vGPCR) is a highly constitutively active G protein-coupled receptor encoded by HHV8 that is regulated both positively and negatively by endogenous chemokines. When expressed in transgenic mice, this chemokine receptor induces an angioproliferative disease closely resembling Kaposi sarcoma (KS). Here we demonstrate that several lines of mice carrying mutated receptors deficient in either constitutive activity or chemokine regulation fail to develop KS-like disease. In addition, animals expressing a receptor that preserves chemokine binding and constitutive activity but that does not respond to agonist stimulation have a much lower incidence of angiogenic lesions and tumors. These results indicate that induction of the KS-like disease in transgenic mice by ORF74 requires not only high constitutive signaling activity but also modulation of this activity by endogenous chemokines. |
| Keywords: | Amino Acid Sequence, COS Cells, Chemokines, Ligands, Molecular Sequence Data, Pathologic Neovascularization, Chemokine Receptors, Kaposi Sarcoma, Signal Transduction, Viral Proteins, Animals, Mice |
| Source: | Journal of Clinical Investigation |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Volume: | 108 |
| Number: | 12 |
| Page Range: | 1789-1796 |
| Date: | December 2001 |
| Official Publication: | https://doi.org/10.1172/JCI13622 |
| PubMed: | View item in PubMed |
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