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IQGAP1 Is a Novel CXCR2-Interacting Protein and Essential Component of the “Chemosynapse”
BACKGROUND: Chemotaxis is essential for a number of physiological processes including leukocyte recruitment. Chemokines initiate intracellular signaling pathways necessary for chemotaxis through binding seven transmembrane G protein-couple receptors. Little is known about the proteins that interact...
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/PMC3158102/ https://www.ncbi.nlm.nih.gov/pubmed/21876773 http://dx.doi.org/10.1371/journal.pone.0023813 |
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author | Neel, Nicole F. Sai, Jiqing Ham, Amy-Joan L. Sobolik-Delmaire, Tammy Mernaugh, Raymond L. Richmond, Ann |
author_facet | Neel, Nicole F. Sai, Jiqing Ham, Amy-Joan L. Sobolik-Delmaire, Tammy Mernaugh, Raymond L. Richmond, Ann |
author_sort | Neel, Nicole F. |
collection | PubMed |
description | BACKGROUND: Chemotaxis is essential for a number of physiological processes including leukocyte recruitment. Chemokines initiate intracellular signaling pathways necessary for chemotaxis through binding seven transmembrane G protein-couple receptors. Little is known about the proteins that interact with the intracellular domains of chemokine receptors to initiate cellular signaling upon ligand binding. CXCR2 is a major chemokine receptor expressed on several cell types, including endothelial cells and neutrophils. We hypothesize that multiple proteins interact with the intracellular domains of CXCR2 upon ligand stimulation and these interactions comprise a “chemosynapse”, and play important roles in transducing CXCR2 mediated signaling processes. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to define the complex of proteins that assemble upon CXCR2 activation to relay signals from activated chemokine receptors, a proteomics approach was employed to identify proteins that co-associate with CXCR2 with or without ligand stimulation. The components of the CXCR2 “chemosynapse” are involved in processes ranging from intracellular trafficking to cytoskeletal modification. IQ motif containing GTPase activating protein 1 (IQGAP1) was among the novel proteins identified to interact directly with CXCR2. Herein, we demonstrate that CXCR2 co-localizes with IQGAP1 at the leading edge of polarized human neutrophils and CXCR2 expressing differentiated HL-60 cells. Moreover, amino acids 1-160 of IQGAP1 directly interact with the carboxyl-terminal domain of CXCR2 and stimulation with CXCL8 enhances IQGAP1 association with Cdc42. CONCLUSIONS: Our studies indicate that IQGAP1 is a novel essential component of the CXCR2 “chemosynapse”. |
format | Online Article Text |
id | pubmed-3158102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31581022011-08-29 IQGAP1 Is a Novel CXCR2-Interacting Protein and Essential Component of the “Chemosynapse” Neel, Nicole F. Sai, Jiqing Ham, Amy-Joan L. Sobolik-Delmaire, Tammy Mernaugh, Raymond L. Richmond, Ann PLoS One Research Article BACKGROUND: Chemotaxis is essential for a number of physiological processes including leukocyte recruitment. Chemokines initiate intracellular signaling pathways necessary for chemotaxis through binding seven transmembrane G protein-couple receptors. Little is known about the proteins that interact with the intracellular domains of chemokine receptors to initiate cellular signaling upon ligand binding. CXCR2 is a major chemokine receptor expressed on several cell types, including endothelial cells and neutrophils. We hypothesize that multiple proteins interact with the intracellular domains of CXCR2 upon ligand stimulation and these interactions comprise a “chemosynapse”, and play important roles in transducing CXCR2 mediated signaling processes. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to define the complex of proteins that assemble upon CXCR2 activation to relay signals from activated chemokine receptors, a proteomics approach was employed to identify proteins that co-associate with CXCR2 with or without ligand stimulation. The components of the CXCR2 “chemosynapse” are involved in processes ranging from intracellular trafficking to cytoskeletal modification. IQ motif containing GTPase activating protein 1 (IQGAP1) was among the novel proteins identified to interact directly with CXCR2. Herein, we demonstrate that CXCR2 co-localizes with IQGAP1 at the leading edge of polarized human neutrophils and CXCR2 expressing differentiated HL-60 cells. Moreover, amino acids 1-160 of IQGAP1 directly interact with the carboxyl-terminal domain of CXCR2 and stimulation with CXCL8 enhances IQGAP1 association with Cdc42. CONCLUSIONS: Our studies indicate that IQGAP1 is a novel essential component of the CXCR2 “chemosynapse”. Public Library of Science 2011-08-18 /pmc/articles/PMC3158102/ /pubmed/21876773 http://dx.doi.org/10.1371/journal.pone.0023813 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Neel, Nicole F. Sai, Jiqing Ham, Amy-Joan L. Sobolik-Delmaire, Tammy Mernaugh, Raymond L. Richmond, Ann IQGAP1 Is a Novel CXCR2-Interacting Protein and Essential Component of the “Chemosynapse” |
title | IQGAP1 Is a Novel CXCR2-Interacting Protein and Essential Component of the “Chemosynapse” |
title_full | IQGAP1 Is a Novel CXCR2-Interacting Protein and Essential Component of the “Chemosynapse” |
title_fullStr | IQGAP1 Is a Novel CXCR2-Interacting Protein and Essential Component of the “Chemosynapse” |
title_full_unstemmed | IQGAP1 Is a Novel CXCR2-Interacting Protein and Essential Component of the “Chemosynapse” |
title_short | IQGAP1 Is a Novel CXCR2-Interacting Protein and Essential Component of the “Chemosynapse” |
title_sort | iqgap1 is a novel cxcr2-interacting protein and essential component of the “chemosynapse” |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158102/ https://www.ncbi.nlm.nih.gov/pubmed/21876773 http://dx.doi.org/10.1371/journal.pone.0023813 |
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