Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor

Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor

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 t...

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Main Authors: Geras-Raaka, Elizabeth, Varma, Anjali, Ho, Hao, Clark-Lewis, Ian, Gershengorn, Marvin C.
Format: Online
Language:English
Published: The Rockefeller University Press 1998
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212452/
id pubmed-2212452
recordtype oai_dc
spelling pubmed-22124522008-04-16 Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor Geras-Raaka, Elizabeth Varma, Anjali Ho, Hao Clark-Lewis, Ian Gershengorn, Marvin C. Brief Definitive Reports 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)-γ–inducible protein 10 (HuIP-10), a C-X-C chemokine, specifically inhibits signaling of KSHV-GPCR. In contrast, monokine induced by IFN-γ (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. The Rockefeller University Press 1998-07-20 /pmc/articles/PMC2212452/ /pubmed/9670053 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Geras-Raaka, Elizabeth
Varma, Anjali
Ho, Hao
Clark-Lewis, Ian
Gershengorn, Marvin C.
spellingShingle Geras-Raaka, Elizabeth
Varma, Anjali
Ho, Hao
Clark-Lewis, Ian
Gershengorn, Marvin C.
Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor
author_facet Geras-Raaka, Elizabeth
Varma, Anjali
Ho, Hao
Clark-Lewis, Ian
Gershengorn, Marvin C.
author_sort Geras-Raaka, Elizabeth
title Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor
title_short Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor
title_full Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor
title_fullStr Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor
title_full_unstemmed Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor
title_sort human interferon-γ–inducible protein 10 (ip-10) inhibits constitutive signaling of kaposi's sarcoma–associated herpesvirus g protein–coupled receptor
description 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)-γ–inducible protein 10 (HuIP-10), a C-X-C chemokine, specifically inhibits signaling of KSHV-GPCR. In contrast, monokine induced by IFN-γ (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.
publisher The Rockefeller University Press
publishDate 1998
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212452/
_version_ 1611434214366904320

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