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J. Exp. Med.,
Volume 188, Number 2, July 20, 1998 405-408
-inducible Protein 10 (IP-10) Inhibits
Constitutive Signaling of Kaposi's Sarcoma-associated
Herpesvirus G Protein-coupled Receptor
By

From the * Division of Molecular Medicine, Department of Medicine, Cornell University Medical
College and The New York Hospital, New York 10021; and the A G protein-coupled receptor (GPCR) is encoded within the genome of Kaposi's sarcoma-
associated herpesvirus (KSHV)/human herpesvirus 8, a virus that may be involved in the pathogenesis of Kaposi's sarcoma and primary effusion lymphomas. KSHV-GPCR exhibits constitutive signaling activity that causes oncogenic transformation. We report that human interferon
(IFN)-
Biomedical Research Centre,
University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada
-inducible protein 10 (HuIP-10), a C-X-C chemokine, specifically inhibits signaling of
KSHV-GPCR. In contrast, monokine induced by IFN-
(HuMig), which like HuIP-10 is an
agonist of C-X-C chemokine receptor 3, does not inhibit KSHV-GPCR signaling. Moreover,
HuIP-10, but not HuMig, inhibits KSHV-GPCR-induced proliferation of NIH 3T3 cells.
These results show that HuIP-10 is an inverse agonist that converts KSHV-GPCR from an active to an inactive state. Thus, a human chemokine inhibits constitutive signaling and cellular proliferation that is mediated by a receptor encoded by a human disease-associated herpesvirus.
;
C-X-C chemokine receptor 3;
inverse agonist;
human herpesvirus 8;
tumorigenesis
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