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siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P(3)-mTOR signaling pathway as a primary regulator of transferrin uptake
BACKGROUND: Iron uptake via endocytosis of iron-transferrin-transferrin receptor complexes is a rate-limiting step for cell growth, viability and proliferation in tumor cells as well as non-transformed cells such as activated lymphocytes. Signaling pathways that regulate transferrin uptake have not...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323231/ https://www.ncbi.nlm.nih.gov/pubmed/17640392 http://dx.doi.org/10.1186/gb-2007-8-7-r142 |
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author | Galvez, Thierry Teruel, Mary N Heo, Won Do Jones, Joshua T Kim, Man Lyang Liou, Jen Myers, Jason W Meyer, Tobias |
author_facet | Galvez, Thierry Teruel, Mary N Heo, Won Do Jones, Joshua T Kim, Man Lyang Liou, Jen Myers, Jason W Meyer, Tobias |
author_sort | Galvez, Thierry |
collection | PubMed |
description | BACKGROUND: Iron uptake via endocytosis of iron-transferrin-transferrin receptor complexes is a rate-limiting step for cell growth, viability and proliferation in tumor cells as well as non-transformed cells such as activated lymphocytes. Signaling pathways that regulate transferrin uptake have not yet been identified. RESULTS: We surveyed the human signaling proteome for regulators that increase or decrease transferrin uptake by screening 1,804 dicer-generated signaling small interfering RNAs using automated quantitative imaging. In addition to known transport proteins, we identified 11 signaling proteins that included a striking signature set for the phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3)-target of rapamycin (mTOR) signaling pathway. We show that the PI3K-mTOR signaling pathway is a positive regulator of transferrin uptake that increases the number of transferrin receptors per endocytic vesicle without affecting endocytosis or recycling rates. CONCLUSION: Our study identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a new regulator of iron-transferrin uptake and serves as a proof-of-concept that targeted RNA interference screens of the signaling proteome provide a powerful and unbiased approach to discover or rank signaling pathways that regulate a particular cell function. |
format | Text |
id | pubmed-2323231 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-23232312008-04-19 siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P(3)-mTOR signaling pathway as a primary regulator of transferrin uptake Galvez, Thierry Teruel, Mary N Heo, Won Do Jones, Joshua T Kim, Man Lyang Liou, Jen Myers, Jason W Meyer, Tobias Genome Biol Research BACKGROUND: Iron uptake via endocytosis of iron-transferrin-transferrin receptor complexes is a rate-limiting step for cell growth, viability and proliferation in tumor cells as well as non-transformed cells such as activated lymphocytes. Signaling pathways that regulate transferrin uptake have not yet been identified. RESULTS: We surveyed the human signaling proteome for regulators that increase or decrease transferrin uptake by screening 1,804 dicer-generated signaling small interfering RNAs using automated quantitative imaging. In addition to known transport proteins, we identified 11 signaling proteins that included a striking signature set for the phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3)-target of rapamycin (mTOR) signaling pathway. We show that the PI3K-mTOR signaling pathway is a positive regulator of transferrin uptake that increases the number of transferrin receptors per endocytic vesicle without affecting endocytosis or recycling rates. CONCLUSION: Our study identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a new regulator of iron-transferrin uptake and serves as a proof-of-concept that targeted RNA interference screens of the signaling proteome provide a powerful and unbiased approach to discover or rank signaling pathways that regulate a particular cell function. BioMed Central 2007 2007-07-19 /pmc/articles/PMC2323231/ /pubmed/17640392 http://dx.doi.org/10.1186/gb-2007-8-7-r142 Text en Copyright © 2007 Galvez et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Galvez, Thierry Teruel, Mary N Heo, Won Do Jones, Joshua T Kim, Man Lyang Liou, Jen Myers, Jason W Meyer, Tobias siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P(3)-mTOR signaling pathway as a primary regulator of transferrin uptake |
title | siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P(3)-mTOR signaling pathway as a primary regulator of transferrin uptake |
title_full | siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P(3)-mTOR signaling pathway as a primary regulator of transferrin uptake |
title_fullStr | siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P(3)-mTOR signaling pathway as a primary regulator of transferrin uptake |
title_full_unstemmed | siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P(3)-mTOR signaling pathway as a primary regulator of transferrin uptake |
title_short | siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P(3)-mTOR signaling pathway as a primary regulator of transferrin uptake |
title_sort | sirna screen of the human signaling proteome identifies the ptdins(3,4,5)p(3)-mtor signaling pathway as a primary regulator of transferrin uptake |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323231/ https://www.ncbi.nlm.nih.gov/pubmed/17640392 http://dx.doi.org/10.1186/gb-2007-8-7-r142 |
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