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Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML
BACKGROUND: Expression of truncated G-CSFR forms in patients with SCN/AML induces hyperproliferation and prolonged cell survival. Previously, we showed that ligand internalization is delayed and degradation of truncated G-CSFR forms is defective in patients with SCN/AML. METHODOLOGY/PRINCIPAL FINDIN...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409964/ https://www.ncbi.nlm.nih.gov/pubmed/18560579 http://dx.doi.org/10.1371/journal.pone.0002452 |
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author | Hunter, Melissa G. McLemore, Morgan Link, Daniel C. Loveland, Megan Copelan, Alexander Avalos, Belinda R. |
author_facet | Hunter, Melissa G. McLemore, Morgan Link, Daniel C. Loveland, Megan Copelan, Alexander Avalos, Belinda R. |
author_sort | Hunter, Melissa G. |
collection | PubMed |
description | BACKGROUND: Expression of truncated G-CSFR forms in patients with SCN/AML induces hyperproliferation and prolonged cell survival. Previously, we showed that ligand internalization is delayed and degradation of truncated G-CSFR forms is defective in patients with SCN/AML. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the potential roles of dileucine and tyrosine-based motifs within the cytoplasmic domain of the G-CSFR in modulating ligand/receptor internalization. Using standard binding assays with radiolabeled ligand and COS-7 cells, substitutions in the dileucine motif or deletion of tyrosine residues in the G-CSFR did not alter internalization. Attachment of the transferrin receptor YTRF internalization motif to a truncated G-CSFR form from a patient with SCN/AML corrected defective internalization, but not receptor degradation suggesting that receptor internalization and degradation occur independently via distinct domains and/or processes. CONCLUSIONS: Our data suggest that distinct domains within the G-CSFR mediate separate processes for receptor internalization and degradation. Our findings using standard binding assays differ from recently published data utilizing flow cytometry. |
format | Text |
id | pubmed-2409964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-24099642008-06-18 Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML Hunter, Melissa G. McLemore, Morgan Link, Daniel C. Loveland, Megan Copelan, Alexander Avalos, Belinda R. PLoS One Research Article BACKGROUND: Expression of truncated G-CSFR forms in patients with SCN/AML induces hyperproliferation and prolonged cell survival. Previously, we showed that ligand internalization is delayed and degradation of truncated G-CSFR forms is defective in patients with SCN/AML. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the potential roles of dileucine and tyrosine-based motifs within the cytoplasmic domain of the G-CSFR in modulating ligand/receptor internalization. Using standard binding assays with radiolabeled ligand and COS-7 cells, substitutions in the dileucine motif or deletion of tyrosine residues in the G-CSFR did not alter internalization. Attachment of the transferrin receptor YTRF internalization motif to a truncated G-CSFR form from a patient with SCN/AML corrected defective internalization, but not receptor degradation suggesting that receptor internalization and degradation occur independently via distinct domains and/or processes. CONCLUSIONS: Our data suggest that distinct domains within the G-CSFR mediate separate processes for receptor internalization and degradation. Our findings using standard binding assays differ from recently published data utilizing flow cytometry. Public Library of Science 2008-06-18 /pmc/articles/PMC2409964/ /pubmed/18560579 http://dx.doi.org/10.1371/journal.pone.0002452 Text en Hunter 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 Hunter, Melissa G. McLemore, Morgan Link, Daniel C. Loveland, Megan Copelan, Alexander Avalos, Belinda R. Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML |
title | Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML |
title_full | Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML |
title_fullStr | Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML |
title_full_unstemmed | Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML |
title_short | Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML |
title_sort | divergent pathways in cos-7 cells mediate defective internalization and intracellular routing of truncated g-csfr forms in scn/aml |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409964/ https://www.ncbi.nlm.nih.gov/pubmed/18560579 http://dx.doi.org/10.1371/journal.pone.0002452 |
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