The Experts below are selected from a list of 18576 Experts worldwide ranked by ideXlab platform
Ralf Stumm - One of the best experts on this subject based on the ideXlab platform.
-
Regional and cellular localization of the CXCl12/SDF‐1 Chemokine Receptor CXCR7 in the developing and adult rat brain
The Journal of comparative neurology, 2008Co-Authors: Bastian Schönemeier, Stefan Schulz, Volker Hoellt, Angela Kolodziej, Stefan Jacobs, Ralf StummAbstract:The Chemokine stromal cell-derived factor-1 (SDF-1) regulates neuronal development via the Chemokine Receptor CXCR4. In the adult brain the SDF-1/CXCR4 system was implicated in neurogenesis, neuromodulation, brain inflammation, tumor growth, and HIV encephalopathy. Until the recent identification of RDC1/CXCR7 as the second SDF-1 Receptor, CXCR4 was considered to be the only Receptor for SDF-1. Here we provide the first map of CXCR7 mRNA expression in the embryonic and adult rat brain. At embryonic stages, CXCR7 and CXCR4 were codistributed in the germinative zone of the ganglionic eminences, caudate putamen, and along the routes of GABAergic precursors migrating toward the cortex. In the cortex, CXCR7 was identified in GABAergic precursors and in some reelin-expressing Cajal-Retzius cells. Unlike CXCR4, CXCR7 was abundant in neurons forming the cortical plate and sparse in the developing dentate gyrus and cerebellar external germinal layer. In the adult brain, CXCR7 was expressed by blood vessels, pyramidal cells in CA3, and mature dentate gyrus granule cells, which is reminiscent of the SDF-1 pattern. CXCR7 and CXCR4 overlapped in the wall of the four ventricles. Further neuronal structures expressing CXCR7 comprised the olfactory bulb, accumbens shell, supraoptic and ventromedial hypothalamic nuclei, medial thalamus, and brain stem motor nuclei. Also, GLAST-expressing astrocytes showed signals for CXCR7. Thus, CXCR4 and CXCR7 may cooperate or act independently in SDF-1-dependent neuronal development. In mature neurons and blood vessels CXCR7 appears to be the preponderant SDF-1-Receptor. Indexing terms: J. Comp. Neurol. 510:207–220, 2008. © 2008 Wiley-Liss, Inc.
-
regional and cellular localization of the cxcl12 sdf 1 Chemokine Receptor CXCR7 in the developing and adult rat brain
The Journal of Comparative Neurology, 2008Co-Authors: Bastian Schönemeier, Stefan Schulz, Volker Hoellt, Angela Kolodziej, Stefan Jacobs, Ralf StummAbstract:The Chemokine stromal cell-derived factor-1 (SDF-1) regulates neuronal development via the Chemokine Receptor CXCR4. In the adult brain the SDF-1/CXCR4 system was implicated in neurogenesis, neuromodulation, brain inflammation, tumor growth, and HIV encephalopathy. Until the recent identification of RDC1/CXCR7 as the second SDF-1 Receptor, CXCR4 was considered to be the only Receptor for SDF-1. Here we provide the first map of CXCR7 mRNA expression in the embryonic and adult rat brain. At embryonic stages, CXCR7 and CXCR4 were codistributed in the germinative zone of the ganglionic eminences, caudate putamen, and along the routes of GABAergic precursors migrating toward the cortex. In the cortex, CXCR7 was identified in GABAergic precursors and in some reelin-expressing Cajal-Retzius cells. Unlike CXCR4, CXCR7 was abundant in neurons forming the cortical plate and sparse in the developing dentate gyrus and cerebellar external germinal layer. In the adult brain, CXCR7 was expressed by blood vessels, pyramidal cells in CA3, and mature dentate gyrus granule cells, which is reminiscent of the SDF-1 pattern. CXCR7 and CXCR4 overlapped in the wall of the four ventricles. Further neuronal structures expressing CXCR7 comprised the olfactory bulb, accumbens shell, supraoptic and ventromedial hypothalamic nuclei, medial thalamus, and brain stem motor nuclei. Also, GLAST-expressing astrocytes showed signals for CXCR7. Thus, CXCR4 and CXCR7 may cooperate or act independently in SDF-1-dependent neuronal development. In mature neurons and blood vessels CXCR7 appears to be the preponderant SDF-1-Receptor. Indexing terms: J. Comp. Neurol. 510:207–220, 2008. © 2008 Wiley-Liss, Inc.
-
enhanced expression of the cxcl12 sdf 1 Chemokine Receptor CXCR7 after cerebral ischemia in the rat brain
Journal of Neuroimmunology, 2008Co-Authors: Bastian Schönemeier, Stefan Schulz, Volker Hoellt, Ralf StummAbstract:Expression patterns of the second SDF-1 Receptor RDC1/CXCR7 were examined after focal ischemia in rats using in situ hybridization. CXCR7 mRNA was identified in the ventricle walls as well as neuronal, astroglial, and vascular cells. After ischemia, intact cortical regions showed a rapid, 4 days-lasting increase in neuronal CXCR7 expression. In the ischemic tissue CXCR7 expression was scarce and associated with blood vessels. Between days 2 and 10 after ischemia-onset, SDF-1 expression increased strongly in the peri-infarct and infarct region, which was accompanied by the appearance of numerous CXCR4-expressing but not CXCR7-expressing cells. These patterns suggest that SDF-1 may influence vascular, astroglial, and neuronal functions via CXCR7 and mediate cell recruitment to ischemic brain areas via CXCR4.
-
Enhanced expression of the CXCl12/SDF-1 Chemokine Receptor CXCR7 after cerebral ischemia in the rat brain.
Journal of neuroimmunology, 2008Co-Authors: Bastian Schönemeier, Stefan Schulz, Volker Hoellt, Ralf StummAbstract:Expression patterns of the second SDF-1 Receptor RDC1/CXCR7 were examined after focal ischemia in rats using in situ hybridization. CXCR7 mRNA was identified in the ventricle walls as well as neuronal, astroglial, and vascular cells. After ischemia, intact cortical regions showed a rapid, 4 days-lasting increase in neuronal CXCR7 expression. In the ischemic tissue CXCR7 expression was scarce and associated with blood vessels. Between days 2 and 10 after ischemia-onset, SDF-1 expression increased strongly in the peri-infarct and infarct region, which was accompanied by the appearance of numerous CXCR4-expressing but not CXCR7-expressing cells. These patterns suggest that SDF-1 may influence vascular, astroglial, and neuronal functions via CXCR7 and mediate cell recruitment to ischemic brain areas via CXCR4.
Hyo Jin Lee - One of the best experts on this subject based on the ideXlab platform.
-
CXCR7 promotes migration and invasion in head and neck squamous cell carcinoma by upregulating TGF-β1/Smad2/3 signaling.
Scientific reports, 2019Co-Authors: Nayoung Kim, Ik-chan Song, Hyewon Ryu, Solbi Kim, Mina Joo, Heung Jin Jeon, Myung-won Lee, Mi-na Kim, Jin-man Kim, Hyo Jin LeeAbstract:The Chemokine Receptor CXCR7 has been suggested to play important roles in the progression of several types of cancers. However, few studies have investigated the biological roles of CXCR7 in head and neck squamous cell carcinoma (HNSCC). CXCR7 expression and its clinical implications were examined in 103 HNSCC tissues using immunohistochemistry (IHC). The biological roles and mechanisms of CXCR7-mediated signaling pathways were investigated in HNSCC cells through CXCR7 overexpression in vitro and in vivo. High expression of CXCR7 was significantly associated with tumor size (P = 0.007), lymph node metastasis (P = 0.004), and stage (P = 0.020) in HNSCC. Overexpression of CXCR7 in HNSCC cells enhanced cell migration and invasion in vitro and promoted lymph node metastasis in vivo. CXCR7 also induced epithelial-mesenchymal transition through PI3K/AKT. CXCR7 increased secretion of transforming growth factor-β1 (TGF-β1) and promoted EMT through phosphorylated Smad2/3. Taken together, our results provide functional and mechanistic roles of CXCR7 as a master regulator of oncogenic TGF-β1/Smad2/3 signaling in HNSCC, suggesting that CXCR7 might be a therapeutic target for the treatment of HNSCC.
-
Abstract 2032: CXCR7 promotes the migration and invasion of head and neck squamous cell carcinoma through Smad2/Akt signaling
Tumor Biology, 2018Co-Authors: Nayoung Kim, Hyewon Ryu, Solbi Kim, Hyo Jin LeeAbstract:Background: The Chemokine Receptor, CXCR7, has been shown to play an important role in the progression of several types of cancer. However, there have been few reports on the biological role of CXCR7 in head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the functional role of CXCR7 and the underlying molecular mechanism of disease progression in HNSCC. Methods: We characterized the expression of CXCR7 in tumor specimens from patients with HNSCC. The biological functions of CXCR7- and CXCR7-mediated signaling pathways were investigated in HNSCC cell lines with CXCR7 overexpression and treatment of SDF-1α, a major ligand of CXCR7, as well as knockdown of CXCR7. Results: CXCR7 was differentially expressed in human HNSCC patients. High expression of CXCR7 was associated with an aggressive tumor behavior. Overexpression of CXCR7 dramatically promoted cell migration and invasion in HNSCC cells, although it was not involved in cell proliferation and colony formation. CXCR7 knockdown using siRNA in HNSCC cells recovered the cell migratory and invasive behavior of HNSCC cells. CXCR7 overexpression also induced the epithelial-mesenchymal transition. Vimentin, Slug, and Twist were increased but E-cadherin and Ep-CAM were decreased by CXCR7 expression. Akt phosphorylation and Smad2 signaling activation were induced in HNSCC cells with CXCR7 overexpression. Treatment with a PI3K inhibitor reduced Slug and Twist levels while suppression of Smad2 signaling by siRNA reduced Akt phosphorylation, as well as Slug and Twist. Furthermore, inhibition of Smad2 decreased tumor cell migration and invasion in HNSCC. Conclusions: CXCR7 contributed to cell migration and invasion of HNSCC through the Smad2/Akt signaling axis, suggesting that CXCR7 might be a therapeutic target for the treatment of HNSCC. Citation Format: Nayoung Kim, Solbi Kim, Hyewon Ryu, Hyo Jin Lee. CXCR7 promotes the migration and invasion of head and neck squamous cell carcinoma through Smad2/Akt signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2032.
-
Expression and functional roles of the Chemokine Receptor CXCR7 in acute myeloid leukemia cells.
Blood research, 2015Co-Authors: Ha-yon Kim, So Yeon Lee, Deog-young Kim, Ji-young Moon, Yoon Seok Choi, Ik-chan Song, Hyo Jin Lee, Hwan Jung Yun, Samyong KimAbstract:Background The C-X-C Chemokine Receptor 7 (CXCR7) has been shown to be a decoy Receptor for CXCR4 in certain cell types. We investigated the expression status and functional roles of CXCR7 in acute myeloid leukemia (AML) cells in vitro.
-
Abstract 1201: Hypoxia promotes not CXCR7 but CXCR4 expression and its biological activity in gastric cancer cell through activation of hypoxia-inducible factor-1β
Molecular and Cellular Biology, 2012Co-Authors: Hyo Jin Lee, Ha-yon Kim, Hwan Jung Yoon, Samyong KimAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: The Chemokine Receptor, CXCR4 and CXCR7, which bind with high affinity same Chemokine CXCL12/SDF-1, are associated with the biological behavior in several kinds of cancer, but few studies have addressed the expression and regulation of CXCR4 and CXCR7 in gastric cancer. Methods: Gastric cancer cell line KATO III was subjected to hypoxia or normoxia. The expression of CXCR4 and CXCR7 were investigated using RT-PCR, Westerning blotting, and flow cytometry before and after hypoxic conditioning. The regulation of CXCR4 and CXCR7, and their biological effects by hypoxia were evaluated using gastric cancer cells transfected with hypoxia-inducible factor (HIF)-1α shRNA. Result: mRNA and proteins of both CXCR4 and CXCR7 were detectable by RT-PCR and Western blot analysis, respectively, in KATO III cells. A small population of KATO III cells expressed membrane CXCR4 and CXCR7 as determined by flow cytometry. Hypoxia up-regulated CXCR4 proteins and enhanced membrane expression of CXCR4 in human gastric cancer KATO III cells, which constitutively expressed membrane CXCR7 and CXCR4 in a steady state, as revealed by Western blotting and flow cytometry, respectively. In contrast, CXCR7 proteins remained unchanged under hypoxia, and promotion of CXCR7 surface expression on KATO III cells could not be demonstrated by flow cytometry. Hypoxia-induced expression of CXCR4 was mediated through activation of HIF-1α with phosphorylation of AKT and ERK, as revealed by HIF-1α knockdown using shRNA. The chemical inducer of HIF-1α, cobalt chloride, induced upregulation of CXCR4 in KATO III cells under normoxic conditions. In addition, KATO III cells exposed to hypoxic condition showed enhanced wound healing, transwell migration, and invasion in response to stromal cell-derived factor (SDF)-1α, a specific ligand for CXCR4. Conclusions: These findings provide evidences for differential regulation and different role of Chemokine Receptor, CXCR7 and CXCR4, in gastric cancer cell in vitro. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1201. doi:1538-7445.AM2012-1201
Andy Chevigné - One of the best experts on this subject based on the ideXlab platform.
-
human herpesvirus 8 encoded Chemokine vccl2 vmip ii is an agonist of the atypical Chemokine Receptor ackr3 CXCR7
Biochemical Pharmacology, 2016Co-Authors: Martyna Szpakowska, Nadine Dupuis, Alessandra Baragli, Manuel Counson, Julien Hanson, Jacques Piette, Andy ChevignéAbstract:The atypical Chemokine Receptor CXCR7/ACKR3 binds two endogenous Chemokines, CXCL12 and CXCL11, and is upregulated in many cancers or following infection by several cancer-inducing viruses, including HHV-8. ACKR3 is a ligand-scavenging Receptor and does not activate the canonical G protein pathways but was proposed to trigger β-arrestin-dependent signaling. Here, we identified the human herpesvirus 8-encoded CC Chemokine vCCL2/vMIP-II as a third high-affinity ligand for ACKR3. vCCL2 acted as partial ACKR3 agonist, inducing β-arrestin recruitment to the Receptor, subsequent reduction of its surface levels and its delivery to endosomes. In addition, ACKR3 reduced vCCL2-triggered MAP kinase and PI3K/Akt signaling through other Chemokine Receptors. Our data suggest that ACKR3 acts as a scavenger Receptor for vCCL2, regulating its availability and activity toward human Receptors, thereby likely controlling its function in HHV-8 infection. Our study provides new insights into the complex crosstalk between viral Chemokines and host Receptors as well as into the biology of ACKR3, this atypical and still enigmatic Receptor.
-
Human herpesvirus 8-encoded Chemokine vCCL2/vMIP-II is an agonist of the atypical Chemokine Receptor ACKR3/CXCR7.
Biochemical pharmacology, 2016Co-Authors: Martyna Szpakowska, Nadine Dupuis, Alessandra Baragli, Manuel Counson, Julien Hanson, Jacques Piette, Andy ChevignéAbstract:The atypical Chemokine Receptor CXCR7/ACKR3 binds two endogenous Chemokines, CXCL12 and CXCL11, and is upregulated in many cancers or following infection by several cancer-inducing viruses, including HHV-8. ACKR3 is a ligand-scavenging Receptor and does not activate the canonical G protein pathways but was proposed to trigger β-arrestin-dependent signaling. Here, we identified the human herpesvirus 8-encoded CC Chemokine vCCL2/vMIP-II as a third high-affinity ligand for ACKR3. vCCL2 acted as partial ACKR3 agonist, inducing β-arrestin recruitment to the Receptor, subsequent reduction of its surface levels and its delivery to endosomes. In addition, ACKR3 reduced vCCL2-triggered MAP kinase and PI3K/Akt signaling through other Chemokine Receptors. Our data suggest that ACKR3 acts as a scavenger Receptor for vCCL2, regulating its availability and activity toward human Receptors, thereby likely controlling its function in HHV-8 infection. Our study provides new insights into the complex crosstalk between viral Chemokines and host Receptors as well as into the biology of ACKR3, this atypical and still enigmatic Receptor.
Bastian Schönemeier - One of the best experts on this subject based on the ideXlab platform.
-
Regional and cellular localization of the CXCl12/SDF‐1 Chemokine Receptor CXCR7 in the developing and adult rat brain
The Journal of comparative neurology, 2008Co-Authors: Bastian Schönemeier, Stefan Schulz, Volker Hoellt, Angela Kolodziej, Stefan Jacobs, Ralf StummAbstract:The Chemokine stromal cell-derived factor-1 (SDF-1) regulates neuronal development via the Chemokine Receptor CXCR4. In the adult brain the SDF-1/CXCR4 system was implicated in neurogenesis, neuromodulation, brain inflammation, tumor growth, and HIV encephalopathy. Until the recent identification of RDC1/CXCR7 as the second SDF-1 Receptor, CXCR4 was considered to be the only Receptor for SDF-1. Here we provide the first map of CXCR7 mRNA expression in the embryonic and adult rat brain. At embryonic stages, CXCR7 and CXCR4 were codistributed in the germinative zone of the ganglionic eminences, caudate putamen, and along the routes of GABAergic precursors migrating toward the cortex. In the cortex, CXCR7 was identified in GABAergic precursors and in some reelin-expressing Cajal-Retzius cells. Unlike CXCR4, CXCR7 was abundant in neurons forming the cortical plate and sparse in the developing dentate gyrus and cerebellar external germinal layer. In the adult brain, CXCR7 was expressed by blood vessels, pyramidal cells in CA3, and mature dentate gyrus granule cells, which is reminiscent of the SDF-1 pattern. CXCR7 and CXCR4 overlapped in the wall of the four ventricles. Further neuronal structures expressing CXCR7 comprised the olfactory bulb, accumbens shell, supraoptic and ventromedial hypothalamic nuclei, medial thalamus, and brain stem motor nuclei. Also, GLAST-expressing astrocytes showed signals for CXCR7. Thus, CXCR4 and CXCR7 may cooperate or act independently in SDF-1-dependent neuronal development. In mature neurons and blood vessels CXCR7 appears to be the preponderant SDF-1-Receptor. Indexing terms: J. Comp. Neurol. 510:207–220, 2008. © 2008 Wiley-Liss, Inc.
-
regional and cellular localization of the cxcl12 sdf 1 Chemokine Receptor CXCR7 in the developing and adult rat brain
The Journal of Comparative Neurology, 2008Co-Authors: Bastian Schönemeier, Stefan Schulz, Volker Hoellt, Angela Kolodziej, Stefan Jacobs, Ralf StummAbstract:The Chemokine stromal cell-derived factor-1 (SDF-1) regulates neuronal development via the Chemokine Receptor CXCR4. In the adult brain the SDF-1/CXCR4 system was implicated in neurogenesis, neuromodulation, brain inflammation, tumor growth, and HIV encephalopathy. Until the recent identification of RDC1/CXCR7 as the second SDF-1 Receptor, CXCR4 was considered to be the only Receptor for SDF-1. Here we provide the first map of CXCR7 mRNA expression in the embryonic and adult rat brain. At embryonic stages, CXCR7 and CXCR4 were codistributed in the germinative zone of the ganglionic eminences, caudate putamen, and along the routes of GABAergic precursors migrating toward the cortex. In the cortex, CXCR7 was identified in GABAergic precursors and in some reelin-expressing Cajal-Retzius cells. Unlike CXCR4, CXCR7 was abundant in neurons forming the cortical plate and sparse in the developing dentate gyrus and cerebellar external germinal layer. In the adult brain, CXCR7 was expressed by blood vessels, pyramidal cells in CA3, and mature dentate gyrus granule cells, which is reminiscent of the SDF-1 pattern. CXCR7 and CXCR4 overlapped in the wall of the four ventricles. Further neuronal structures expressing CXCR7 comprised the olfactory bulb, accumbens shell, supraoptic and ventromedial hypothalamic nuclei, medial thalamus, and brain stem motor nuclei. Also, GLAST-expressing astrocytes showed signals for CXCR7. Thus, CXCR4 and CXCR7 may cooperate or act independently in SDF-1-dependent neuronal development. In mature neurons and blood vessels CXCR7 appears to be the preponderant SDF-1-Receptor. Indexing terms: J. Comp. Neurol. 510:207–220, 2008. © 2008 Wiley-Liss, Inc.
-
enhanced expression of the cxcl12 sdf 1 Chemokine Receptor CXCR7 after cerebral ischemia in the rat brain
Journal of Neuroimmunology, 2008Co-Authors: Bastian Schönemeier, Stefan Schulz, Volker Hoellt, Ralf StummAbstract:Expression patterns of the second SDF-1 Receptor RDC1/CXCR7 were examined after focal ischemia in rats using in situ hybridization. CXCR7 mRNA was identified in the ventricle walls as well as neuronal, astroglial, and vascular cells. After ischemia, intact cortical regions showed a rapid, 4 days-lasting increase in neuronal CXCR7 expression. In the ischemic tissue CXCR7 expression was scarce and associated with blood vessels. Between days 2 and 10 after ischemia-onset, SDF-1 expression increased strongly in the peri-infarct and infarct region, which was accompanied by the appearance of numerous CXCR4-expressing but not CXCR7-expressing cells. These patterns suggest that SDF-1 may influence vascular, astroglial, and neuronal functions via CXCR7 and mediate cell recruitment to ischemic brain areas via CXCR4.
-
Enhanced expression of the CXCl12/SDF-1 Chemokine Receptor CXCR7 after cerebral ischemia in the rat brain.
Journal of neuroimmunology, 2008Co-Authors: Bastian Schönemeier, Stefan Schulz, Volker Hoellt, Ralf StummAbstract:Expression patterns of the second SDF-1 Receptor RDC1/CXCR7 were examined after focal ischemia in rats using in situ hybridization. CXCR7 mRNA was identified in the ventricle walls as well as neuronal, astroglial, and vascular cells. After ischemia, intact cortical regions showed a rapid, 4 days-lasting increase in neuronal CXCR7 expression. In the ischemic tissue CXCR7 expression was scarce and associated with blood vessels. Between days 2 and 10 after ischemia-onset, SDF-1 expression increased strongly in the peri-infarct and infarct region, which was accompanied by the appearance of numerous CXCR4-expressing but not CXCR7-expressing cells. These patterns suggest that SDF-1 may influence vascular, astroglial, and neuronal functions via CXCR7 and mediate cell recruitment to ischemic brain areas via CXCR4.
Martyna Szpakowska - One of the best experts on this subject based on the ideXlab platform.
-
human herpesvirus 8 encoded Chemokine vccl2 vmip ii is an agonist of the atypical Chemokine Receptor ackr3 CXCR7
Biochemical Pharmacology, 2016Co-Authors: Martyna Szpakowska, Nadine Dupuis, Alessandra Baragli, Manuel Counson, Julien Hanson, Jacques Piette, Andy ChevignéAbstract:The atypical Chemokine Receptor CXCR7/ACKR3 binds two endogenous Chemokines, CXCL12 and CXCL11, and is upregulated in many cancers or following infection by several cancer-inducing viruses, including HHV-8. ACKR3 is a ligand-scavenging Receptor and does not activate the canonical G protein pathways but was proposed to trigger β-arrestin-dependent signaling. Here, we identified the human herpesvirus 8-encoded CC Chemokine vCCL2/vMIP-II as a third high-affinity ligand for ACKR3. vCCL2 acted as partial ACKR3 agonist, inducing β-arrestin recruitment to the Receptor, subsequent reduction of its surface levels and its delivery to endosomes. In addition, ACKR3 reduced vCCL2-triggered MAP kinase and PI3K/Akt signaling through other Chemokine Receptors. Our data suggest that ACKR3 acts as a scavenger Receptor for vCCL2, regulating its availability and activity toward human Receptors, thereby likely controlling its function in HHV-8 infection. Our study provides new insights into the complex crosstalk between viral Chemokines and host Receptors as well as into the biology of ACKR3, this atypical and still enigmatic Receptor.
-
Human herpesvirus 8-encoded Chemokine vCCL2/vMIP-II is an agonist of the atypical Chemokine Receptor ACKR3/CXCR7.
Biochemical pharmacology, 2016Co-Authors: Martyna Szpakowska, Nadine Dupuis, Alessandra Baragli, Manuel Counson, Julien Hanson, Jacques Piette, Andy ChevignéAbstract:The atypical Chemokine Receptor CXCR7/ACKR3 binds two endogenous Chemokines, CXCL12 and CXCL11, and is upregulated in many cancers or following infection by several cancer-inducing viruses, including HHV-8. ACKR3 is a ligand-scavenging Receptor and does not activate the canonical G protein pathways but was proposed to trigger β-arrestin-dependent signaling. Here, we identified the human herpesvirus 8-encoded CC Chemokine vCCL2/vMIP-II as a third high-affinity ligand for ACKR3. vCCL2 acted as partial ACKR3 agonist, inducing β-arrestin recruitment to the Receptor, subsequent reduction of its surface levels and its delivery to endosomes. In addition, ACKR3 reduced vCCL2-triggered MAP kinase and PI3K/Akt signaling through other Chemokine Receptors. Our data suggest that ACKR3 acts as a scavenger Receptor for vCCL2, regulating its availability and activity toward human Receptors, thereby likely controlling its function in HHV-8 infection. Our study provides new insights into the complex crosstalk between viral Chemokines and host Receptors as well as into the biology of ACKR3, this atypical and still enigmatic Receptor.