The small GTPase Rac1 links the Kaposi sarcoma-associated herpesvirus vGPCR to cytokine secretion and paracrine neoplasia.

@article{Montaner2004TheSG,
  title={The small GTPase Rac1 links the Kaposi sarcoma-associated herpesvirus vGPCR to cytokine secretion and paracrine neoplasia.},
  author={S. Montaner and A. Sodhi and J. Servitja and Amanda K Ramsdell and A. Barac and E. Sawai and J. Gutkind},
  journal={Blood},
  year={2004},
  volume={104 9},
  pages={
          2903-11
        }
}
Kaposi sarcoma (KS) is a multifocal angioproliferative neoplasm strictly dependent on angiogenic growth factors and cytokines and invariably associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV or HHV8). A G protein-coupled receptor encoded by KSHV (vGPCR) is able to initiate KS-like tumors when targeted to the vascular endothelium of mice. Analogous to human KS, vGPCR sarcomagenesis involves the paracrine secretion of angiogenic growth factors and proinflammatory… Expand
YGLF motif in the Kaposi sarcoma herpes virus G-protein-coupled receptor adjusts NF-κB activation and paracrine actions
TLDR
It is shown that vGPCR expression contributes to nuclear factor-κB-dependent cellular survival in both PEL cells and primary B cells from HIV-negative KS patients, raising the possibility that KSHV-infected B-lymphocytes use vG PCR to impact ultimately the immune response and communication within the tumour microenvironment in KSHv-associated pathologies. Expand
B-Raf-dependent expression of vascular endothelial growth factor-A in Kaposi sarcoma-associated herpesvirus-infected human B cells.
TLDR
The ability of Raf-associated signaling to play a role in the expression of VEGF-A in KSHV-infected hematopoietic cells is reported for the first time. Expand
CADM1 is essential for KSHV-encoded vGPCR-and vFLIP-mediated chronic NF-κB activation
TLDR
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Kaposi's Sarcoma-Associated Herpesvirus K7 Induces Viral G Protein-Coupled Receptor Degradation and Reduces Its Tumorigenicity
TLDR
A viral factor is defined that negatively regulates vGPCR protein expression and a post-translational event is revealed that modulates GPCR-dependent transformation and tumorigenicity. Expand
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TLDR
Techniques and strategies used to study the unique properties and functions of vGPCR and its role in oncogenesis of Kaposi's sarcoma are described. Expand
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TLDR
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TLDR
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Inhibition of Heme Oxygenase-1 Interferes with the Transforming Activity of the Kaposi Sarcoma Herpesvirusencoded G Protein-coupled Receptor*♦
TLDR
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The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor.
TLDR
It is demonstrated that Kaposi's sarcomagenesis involves stimulation of tuberin (TSC2) phosphorylation by vGPCR, promoting the activation of mTOR through both direct and paracrine mechanisms, and implicate mTOR in KS initiation. Expand
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The Kaposi's Sarcoma-Associated Herpesvirus G Protein-Coupled Receptor Has Broad Signaling Effects in Primary Effusion Lymphoma Cells
TLDR
KSHV/human herpesvirus 8 [HHV-8], a gamma-2-herpesvirus responsible for Kaposi's sarcoma as well as primary effusion lymphoma, is a lymphotropic virus that has pirated many mammalian genes involved in inflammation, cell cycle control, and angiogenesis and vGPCR is a homologue of the human interleukin-8 receptor. Expand
Human Herpesvirus 8-Encoded vGPCR Activates Nuclear Factor of Activated T Cells and Collaborates with Human Immunodeficiency Virus Type 1 Tat
TLDR
The data further support the idea that vGPCR contributes to the pathogenesis of KS by a paracrine mechanism and, in addition, provide the first evidence of collaboration between an HIV-1 protein and an HHV-8 protein. Expand
G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator
TLDR
It is concluded that the KSHV G-protein-coupled receptor is a viral oncogene that can exploit cell signalling pathways to induce transformation and angiogenesis in K SHV-mediated oncogenesis. Expand
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TLDR
The data suggest that Kaposi’s sarcoma-associated herpesvirus results in part from KSHV-GPCR induction of proinflammatory cytokine and growth factor gene expression, mediated by a signaling determinant within the last five amino acids of the C terminus, a domain that is also critical for direct cell transformation. Expand
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TLDR
It is shown that expression of ORF74 in a minority of cells in KS lesions could influence uninfected cells or latently infected cells via autocrine and paracrine mechanisms, thereby contributing to KS pathogenesis. Expand
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TLDR
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TLDR
It is concluded that vFLIP, in addition to its known effects on NF-κB activation, also modulates the JNK/AP1 pathway and induces gene expression from the cIL-6 promoter in a JNK-AP1-dependent fashion. Expand
The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1α
TLDR
These findings suggest that the KSHV GPCR oncogene subverts convergent physiological pathways leading to angiogenesis and provide the first insight into a mechanism whereby growth factors and oncogenes acting upstream from MAPK, as well as inflammatory cytokines and cellular stresses that activate p38, can interact with the hypoxia-dependent machinery of angiynthesis. Expand
The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1alpha.
TLDR
These findings suggest that the KSHV GPCR oncogene subverts convergent physiological pathways leading to angiogenesis and provide the first insight into a mechanism whereby growth factors and oncogenes acting upstream from MAPK, as well as inflammatory cytokines and cellular stresses that activate p38, can interact with the hypoxia-dependent machinery of angiynthesis. Expand
The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promotes endothelial cell survival through the activation of Akt/protein kinase B.
TLDR
It is found that KSHV-GPCR is able to protect human umbilical vein endothelial cells from the apoptosis induced by serum deprivation and that both wortmannin and the expression of a kinase-deficient Akt K179M mutant are able to block this effect. Expand
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