Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR

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The G protein-coupled receptor oncogene (vGPCR) of the Kaposi's sarcoma (KS) associated herpesvirus (KSHV), an oncovirus implicated in angioproliferative neoplasms, induces angiogenesis by VEGF secretion. Accordingly, we found that expression of vGPCR in human umbilical vein endothelial cells (...

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Autores principales:	Bais, C., Van Geelen, A., Eroles, P., Mutlu, A., Chiozzini, C., Dias, S., Silverstein, R.L., Rafii, S., Mesri, E.A.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2003
Materias:	G protein coupled receptor vasculotropin receptor 2 virus protein AKT1 protein, human chemokine receptor endothelial cell growth factor G protein coupled receptor, Human herpesvirus 8 G protein-coupled receptor, Human herpesvirus 8 lymphokine oncoprotein phosphatidylinositol 3 kinase protein kinase B protein serine threonine kinase signal peptide telomerase vasculotropin vasculotropin A apoptosis article association autocrine effect cell immortalization endothelium cell human human cell Human herpesvirus 8 priority journal protein expression protein function signal transduction telomere umbilical vein cell culture cell transformation genetics Kaposi sarcoma metabolism pathogenicity pathology phosphorylation physiology Retrovirus vascular endothelium virology Herpesviridae Oncovirinae Papovaviridae 1-Phosphatidylinositol 3-Kinase Apoptosis Cell Transformation, Neoplastic Cells, Cultured Endothelial Growth Factors Endothelium, Vascular Herpesvirus 8, Human Humans Intercellular Signaling Peptides and Proteins Lymphokines Phosphorylation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Receptors, Chemokine Retroviridae Sarcoma, Kaposi Signal Transduction Telomerase Telomere Umbilical Veins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factors Viral Proteins
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_15356108_v3_n2_p131_Bais
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paperaa:paper_15356108_v3_n2_p131_Bais2023-06-12T16:50:39Z Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR Cancer Cell 2003;3(2):131-143 Bais, C. Van Geelen, A. Eroles, P. Mutlu, A. Chiozzini, C. Dias, S. Silverstein, R.L. Rafii, S. Mesri, E.A. G protein coupled receptor vasculotropin receptor 2 virus protein AKT1 protein, human chemokine receptor endothelial cell growth factor G protein coupled receptor, Human herpesvirus 8 G protein-coupled receptor, Human herpesvirus 8 lymphokine oncoprotein phosphatidylinositol 3 kinase protein kinase B protein serine threonine kinase signal peptide telomerase vasculotropin vasculotropin A apoptosis article association autocrine effect cell immortalization endothelium cell human human cell Human herpesvirus 8 priority journal protein expression protein function signal transduction telomere umbilical vein cell culture cell transformation genetics Kaposi sarcoma metabolism pathogenicity pathology phosphorylation physiology Retrovirus vascular endothelium virology Herpesviridae Human herpesvirus 8 Oncovirinae Papovaviridae 1-Phosphatidylinositol 3-Kinase Apoptosis Cell Transformation, Neoplastic Cells, Cultured Endothelial Growth Factors Endothelium, Vascular Herpesvirus 8, Human Humans Intercellular Signaling Peptides and Proteins Lymphokines Phosphorylation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Receptors, Chemokine Retroviridae Sarcoma, Kaposi Signal Transduction Telomerase Telomere Umbilical Veins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factors Viral Proteins The G protein-coupled receptor oncogene (vGPCR) of the Kaposi's sarcoma (KS) associated herpesvirus (KSHV), an oncovirus implicated in angioproliferative neoplasms, induces angiogenesis by VEGF secretion. Accordingly, we found that expression of vGPCR in human umbilical vein endothelial cells (HUVEC) leads to immortalization with constitutive VEGF receptor-2/ KDR expression and activation. vGPCR immortalization was associated with anti-senescence mediated by alternative lengthening of telomeres and an anti-apoptotic response mediated by vGPCR constitutive signaling and KDR autocrine signaling leading to activation of the PI3K/AKT pathway. In the presence of the KS growth factor VEGF, this mechanism can sustain suppression of signaling by the immortalizing gene. We conclude that vGPCR can cause an oncogenic immortalizing event and recapitulate aspects of the KS angiogenic phenotype in human endothelial cells, pointing to this gene as a pathogenic determinant of KSHV. Fil:Bais, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Mesri, E.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2003 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15356108_v3_n2_p131_Bais
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	G protein coupled receptor vasculotropin receptor 2 virus protein AKT1 protein, human chemokine receptor endothelial cell growth factor G protein coupled receptor, Human herpesvirus 8 G protein-coupled receptor, Human herpesvirus 8 lymphokine oncoprotein phosphatidylinositol 3 kinase protein kinase B protein serine threonine kinase signal peptide telomerase vasculotropin vasculotropin A apoptosis article association autocrine effect cell immortalization endothelium cell human human cell Human herpesvirus 8 priority journal protein expression protein function signal transduction telomere umbilical vein cell culture cell transformation genetics Kaposi sarcoma metabolism pathogenicity pathology phosphorylation physiology Retrovirus vascular endothelium virology Herpesviridae Human herpesvirus 8 Oncovirinae Papovaviridae 1-Phosphatidylinositol 3-Kinase Apoptosis Cell Transformation, Neoplastic Cells, Cultured Endothelial Growth Factors Endothelium, Vascular Herpesvirus 8, Human Humans Intercellular Signaling Peptides and Proteins Lymphokines Phosphorylation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Receptors, Chemokine Retroviridae Sarcoma, Kaposi Signal Transduction Telomerase Telomere Umbilical Veins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factors Viral Proteins
spellingShingle	G protein coupled receptor vasculotropin receptor 2 virus protein AKT1 protein, human chemokine receptor endothelial cell growth factor G protein coupled receptor, Human herpesvirus 8 G protein-coupled receptor, Human herpesvirus 8 lymphokine oncoprotein phosphatidylinositol 3 kinase protein kinase B protein serine threonine kinase signal peptide telomerase vasculotropin vasculotropin A apoptosis article association autocrine effect cell immortalization endothelium cell human human cell Human herpesvirus 8 priority journal protein expression protein function signal transduction telomere umbilical vein cell culture cell transformation genetics Kaposi sarcoma metabolism pathogenicity pathology phosphorylation physiology Retrovirus vascular endothelium virology Herpesviridae Human herpesvirus 8 Oncovirinae Papovaviridae 1-Phosphatidylinositol 3-Kinase Apoptosis Cell Transformation, Neoplastic Cells, Cultured Endothelial Growth Factors Endothelium, Vascular Herpesvirus 8, Human Humans Intercellular Signaling Peptides and Proteins Lymphokines Phosphorylation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Receptors, Chemokine Retroviridae Sarcoma, Kaposi Signal Transduction Telomerase Telomere Umbilical Veins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factors Viral Proteins Bais, C. Van Geelen, A. Eroles, P. Mutlu, A. Chiozzini, C. Dias, S. Silverstein, R.L. Rafii, S. Mesri, E.A. Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR
topic_facet	G protein coupled receptor vasculotropin receptor 2 virus protein AKT1 protein, human chemokine receptor endothelial cell growth factor G protein coupled receptor, Human herpesvirus 8 G protein-coupled receptor, Human herpesvirus 8 lymphokine oncoprotein phosphatidylinositol 3 kinase protein kinase B protein serine threonine kinase signal peptide telomerase vasculotropin vasculotropin A apoptosis article association autocrine effect cell immortalization endothelium cell human human cell Human herpesvirus 8 priority journal protein expression protein function signal transduction telomere umbilical vein cell culture cell transformation genetics Kaposi sarcoma metabolism pathogenicity pathology phosphorylation physiology Retrovirus vascular endothelium virology Herpesviridae Human herpesvirus 8 Oncovirinae Papovaviridae 1-Phosphatidylinositol 3-Kinase Apoptosis Cell Transformation, Neoplastic Cells, Cultured Endothelial Growth Factors Endothelium, Vascular Herpesvirus 8, Human Humans Intercellular Signaling Peptides and Proteins Lymphokines Phosphorylation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Receptors, Chemokine Retroviridae Sarcoma, Kaposi Signal Transduction Telomerase Telomere Umbilical Veins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factors Viral Proteins
description	The G protein-coupled receptor oncogene (vGPCR) of the Kaposi's sarcoma (KS) associated herpesvirus (KSHV), an oncovirus implicated in angioproliferative neoplasms, induces angiogenesis by VEGF secretion. Accordingly, we found that expression of vGPCR in human umbilical vein endothelial cells (HUVEC) leads to immortalization with constitutive VEGF receptor-2/ KDR expression and activation. vGPCR immortalization was associated with anti-senescence mediated by alternative lengthening of telomeres and an anti-apoptotic response mediated by vGPCR constitutive signaling and KDR autocrine signaling leading to activation of the PI3K/AKT pathway. In the presence of the KS growth factor VEGF, this mechanism can sustain suppression of signaling by the immortalizing gene. We conclude that vGPCR can cause an oncogenic immortalizing event and recapitulate aspects of the KS angiogenic phenotype in human endothelial cells, pointing to this gene as a pathogenic determinant of KSHV.
format	Artículo Artículo publishedVersion
author	Bais, C. Van Geelen, A. Eroles, P. Mutlu, A. Chiozzini, C. Dias, S. Silverstein, R.L. Rafii, S. Mesri, E.A.
author_facet	Bais, C. Van Geelen, A. Eroles, P. Mutlu, A. Chiozzini, C. Dias, S. Silverstein, R.L. Rafii, S. Mesri, E.A.
author_sort	Bais, C.
title	Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR
title_short	Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR
title_full	Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR
title_fullStr	Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR
title_full_unstemmed	Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR
title_sort	kaposi's sarcoma associated herpesvirus g protein-coupled receptor immortalizes human endothelial cells by activation of the vegf receptor-2/ kdr
publishDate	2003
url	http://hdl.handle.net/20.500.12110/paper_15356108_v3_n2_p131_Bais
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Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR

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