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LyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis
SHIP and SHIP-2 are inositol phosphatases that regulate FcγR-mediated phagocytosis through catalytic as well as non-catalytic mechanisms. In this study we have used two-dimensional fluorescence difference gel electrophoresis (DIGE) analysis to identify downstream signaling proteins that uniquely ass...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114867/ https://www.ncbi.nlm.nih.gov/pubmed/21695085 http://dx.doi.org/10.1371/journal.pone.0021175 |
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author | Mehta, Payal Wavreille, Anne-Sophie Justiniano, Steven E. Marsh, Rachel L. Yu, Jianhua Burry, Richard W. Jarjoura, David Eubank, Timothy Caligiuri, Michael A. Butchar, Jonathan P. Tridandapani, Susheela |
author_facet | Mehta, Payal Wavreille, Anne-Sophie Justiniano, Steven E. Marsh, Rachel L. Yu, Jianhua Burry, Richard W. Jarjoura, David Eubank, Timothy Caligiuri, Michael A. Butchar, Jonathan P. Tridandapani, Susheela |
author_sort | Mehta, Payal |
collection | PubMed |
description | SHIP and SHIP-2 are inositol phosphatases that regulate FcγR-mediated phagocytosis through catalytic as well as non-catalytic mechanisms. In this study we have used two-dimensional fluorescence difference gel electrophoresis (DIGE) analysis to identify downstream signaling proteins that uniquely associate with SHIP or SHIP-2 upon FcγR clustering in human monocytes. We identified LyGDI as a binding partner of SHIP, associating inducibly with the SHIP/Grb2/Shc complex. Immunodepletion and competition experiments with recombinant SHIP domains revealed that Grb2 and the proline-rich domain of SHIP were necessary for SHIP-LyGDI association. Functional studies in primary human monocytes showed that LyGDI sequesters Rac in the cytosol, preventing it from localizing to the membrane. Consistent with this, suppression of LyGDI expression resulted in significantly enhanced FcγR-mediated phagocytosis. |
format | Online Article Text |
id | pubmed-3114867 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31148672011-06-21 LyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis Mehta, Payal Wavreille, Anne-Sophie Justiniano, Steven E. Marsh, Rachel L. Yu, Jianhua Burry, Richard W. Jarjoura, David Eubank, Timothy Caligiuri, Michael A. Butchar, Jonathan P. Tridandapani, Susheela PLoS One Research Article SHIP and SHIP-2 are inositol phosphatases that regulate FcγR-mediated phagocytosis through catalytic as well as non-catalytic mechanisms. In this study we have used two-dimensional fluorescence difference gel electrophoresis (DIGE) analysis to identify downstream signaling proteins that uniquely associate with SHIP or SHIP-2 upon FcγR clustering in human monocytes. We identified LyGDI as a binding partner of SHIP, associating inducibly with the SHIP/Grb2/Shc complex. Immunodepletion and competition experiments with recombinant SHIP domains revealed that Grb2 and the proline-rich domain of SHIP were necessary for SHIP-LyGDI association. Functional studies in primary human monocytes showed that LyGDI sequesters Rac in the cytosol, preventing it from localizing to the membrane. Consistent with this, suppression of LyGDI expression resulted in significantly enhanced FcγR-mediated phagocytosis. Public Library of Science 2011-06-14 /pmc/articles/PMC3114867/ /pubmed/21695085 http://dx.doi.org/10.1371/journal.pone.0021175 Text en Mehta et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mehta, Payal Wavreille, Anne-Sophie Justiniano, Steven E. Marsh, Rachel L. Yu, Jianhua Burry, Richard W. Jarjoura, David Eubank, Timothy Caligiuri, Michael A. Butchar, Jonathan P. Tridandapani, Susheela LyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis |
title | LyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis |
title_full | LyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis |
title_fullStr | LyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis |
title_full_unstemmed | LyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis |
title_short | LyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis |
title_sort | lygdi, a novel ship-interacting protein, is a negative regulator of fcγr-mediated phagocytosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114867/ https://www.ncbi.nlm.nih.gov/pubmed/21695085 http://dx.doi.org/10.1371/journal.pone.0021175 |
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