Ubiquitin receptor binding and signaling in primary human leukocytes
Utilizing the human monocyte/macrophage cell line THP1, we recently identified extracellular ubiquitin as an endogenous agonist of the G protein-coupled receptor CXC chemokine receptor (CXCR) 4. Because receptor binding and signaling properties of extracellular ubiquitin have not been evaluated in p...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2010-11-01
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| Series: | Communicative & Integrative Biology |
| Online Access: | https://www.tandfonline.com/doi/10.4161/cib.3.6.13375 |
| _version_ | 1797683819012161536 |
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| author | Vikas Saini Jacqueline Romero Adriano Marchese Matthias Majetschak |
| author_facet | Vikas Saini Jacqueline Romero Adriano Marchese Matthias Majetschak |
| author_sort | Vikas Saini |
| collection | DOAJ |
| description | Utilizing the human monocyte/macrophage cell line THP1, we recently identified extracellular ubiquitin as an endogenous agonist of the G protein-coupled receptor CXC chemokine receptor (CXCR) 4. Because receptor binding and signaling properties of extracellular ubiquitin have not been evaluated in primary human leukocytes, we analyzed its binding characteristics and subsequent Ca2+ signaling in freshly isolated human B-cells, T-cells and monocytes. Ubiquitin binding shows typical receptor binding characteristics and promotes intracellular Ca2+ flux within seconds in all three cell populations. The Kd for the ubiquitin receptor interaction in freshly isolated human monocytes is consistent with the affinity of the ubiquitin CXCR4 interaction that we reported for THP1 cells. As detected in THP1 cells previously, the ubiquitin induced Ca2+ flux can be attenuated with a phospholipase C inhibitor in all primary leukocyte cultures. Our observations further support the finding that ubiquitin is a CXCR4 agonist and demonstrate that extracellular ubiquitin induces physiological relevant signaling events in primary human leukocytes. Although the exact mechanism of the ubiquitin CXCR4 interaction, its receptor selectivity and subsequent signaling events remain to be determined, our findings identify a novel and unexpected biological role of extracellular ubiquitin as an endogenous immune modulator. |
| first_indexed | 2024-03-12T00:21:20Z |
| format | Article |
| id | doaj.art-9ca68987a6724a6e962722719f897042 |
| institution | Directory Open Access Journal |
| issn | 1942-0889 |
| language | English |
| last_indexed | 2024-03-12T00:21:20Z |
| publishDate | 2010-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Communicative & Integrative Biology |
| spelling | doaj.art-9ca68987a6724a6e962722719f8970422023-09-15T13:06:45ZengTaylor & Francis GroupCommunicative & Integrative Biology1942-08892010-11-013660861010.4161/cib.3.6.13375Ubiquitin receptor binding and signaling in primary human leukocytesVikas Saini0Jacqueline Romero1Adriano Marchese2Matthias Majetschak3Burn and Shock Trauma Institute, Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, IL USABurn and Shock Trauma Institute, Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, IL USADepartment of Molecular Pharmacology & Therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, IL USABurn and Shock Trauma Institute, Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, IL USAUtilizing the human monocyte/macrophage cell line THP1, we recently identified extracellular ubiquitin as an endogenous agonist of the G protein-coupled receptor CXC chemokine receptor (CXCR) 4. Because receptor binding and signaling properties of extracellular ubiquitin have not been evaluated in primary human leukocytes, we analyzed its binding characteristics and subsequent Ca2+ signaling in freshly isolated human B-cells, T-cells and monocytes. Ubiquitin binding shows typical receptor binding characteristics and promotes intracellular Ca2+ flux within seconds in all three cell populations. The Kd for the ubiquitin receptor interaction in freshly isolated human monocytes is consistent with the affinity of the ubiquitin CXCR4 interaction that we reported for THP1 cells. As detected in THP1 cells previously, the ubiquitin induced Ca2+ flux can be attenuated with a phospholipase C inhibitor in all primary leukocyte cultures. Our observations further support the finding that ubiquitin is a CXCR4 agonist and demonstrate that extracellular ubiquitin induces physiological relevant signaling events in primary human leukocytes. Although the exact mechanism of the ubiquitin CXCR4 interaction, its receptor selectivity and subsequent signaling events remain to be determined, our findings identify a novel and unexpected biological role of extracellular ubiquitin as an endogenous immune modulator.https://www.tandfonline.com/doi/10.4161/cib.3.6.13375 |
| spellingShingle | Vikas Saini Jacqueline Romero Adriano Marchese Matthias Majetschak Ubiquitin receptor binding and signaling in primary human leukocytes Communicative & Integrative Biology |
| title | Ubiquitin receptor binding and signaling in primary human leukocytes |
| title_full | Ubiquitin receptor binding and signaling in primary human leukocytes |
| title_fullStr | Ubiquitin receptor binding and signaling in primary human leukocytes |
| title_full_unstemmed | Ubiquitin receptor binding and signaling in primary human leukocytes |
| title_short | Ubiquitin receptor binding and signaling in primary human leukocytes |
| title_sort | ubiquitin receptor binding and signaling in primary human leukocytes |
| url | https://www.tandfonline.com/doi/10.4161/cib.3.6.13375 |
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