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Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin)
The organization of the endocytic system into biochemically distinct subcompartments allows for spatial and temporal control of the strength and duration of signaling. Recent work has established that Akt cell survival signaling via the epidermal growth factor receptor (EGFR) occurs from APPL early...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510023/ https://www.ncbi.nlm.nih.gov/pubmed/23051738 http://dx.doi.org/10.1091/mbc.E12-02-0133 |
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author | Beas, Anthony O. Taupin, Vanessa Teodorof, Carmen Nguyen, Lien T. Garcia-Marcos, Mikel Farquhar, Marilyn G. |
author_facet | Beas, Anthony O. Taupin, Vanessa Teodorof, Carmen Nguyen, Lien T. Garcia-Marcos, Mikel Farquhar, Marilyn G. |
author_sort | Beas, Anthony O. |
collection | PubMed |
description | The organization of the endocytic system into biochemically distinct subcompartments allows for spatial and temporal control of the strength and duration of signaling. Recent work has established that Akt cell survival signaling via the epidermal growth factor receptor (EGFR) occurs from APPL early endosomes that mature into early EEA1 endosomes. Less is known about receptor signaling from EEA1 endosomes. We show here that EGF-induced, proliferative signaling occurs from EEA1 endosomes and is regulated by the heterotrimeric G protein Gαs through interaction with the signal transducing protein GIV (also known as Girdin). When Gαs or GIV is depleted, activated EGFR and its adaptors accumulate in EEA1 endosomes, and EGFR signaling is prolonged, EGFR down-regulation is delayed, and cell proliferation is greatly enhanced. Our findings define EEA1 endosomes as major sites for proliferative signaling and establish that Gαs and GIV regulate EEA1 but not APPL endosome maturation and determine the duration and strength of proliferative signaling from this compartment. |
format | Online Article Text |
id | pubmed-3510023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35100232013-02-16 Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin) Beas, Anthony O. Taupin, Vanessa Teodorof, Carmen Nguyen, Lien T. Garcia-Marcos, Mikel Farquhar, Marilyn G. Mol Biol Cell Articles The organization of the endocytic system into biochemically distinct subcompartments allows for spatial and temporal control of the strength and duration of signaling. Recent work has established that Akt cell survival signaling via the epidermal growth factor receptor (EGFR) occurs from APPL early endosomes that mature into early EEA1 endosomes. Less is known about receptor signaling from EEA1 endosomes. We show here that EGF-induced, proliferative signaling occurs from EEA1 endosomes and is regulated by the heterotrimeric G protein Gαs through interaction with the signal transducing protein GIV (also known as Girdin). When Gαs or GIV is depleted, activated EGFR and its adaptors accumulate in EEA1 endosomes, and EGFR signaling is prolonged, EGFR down-regulation is delayed, and cell proliferation is greatly enhanced. Our findings define EEA1 endosomes as major sites for proliferative signaling and establish that Gαs and GIV regulate EEA1 but not APPL endosome maturation and determine the duration and strength of proliferative signaling from this compartment. The American Society for Cell Biology 2012-12-01 /pmc/articles/PMC3510023/ /pubmed/23051738 http://dx.doi.org/10.1091/mbc.E12-02-0133 Text en © 2012 Beas et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Beas, Anthony O. Taupin, Vanessa Teodorof, Carmen Nguyen, Lien T. Garcia-Marcos, Mikel Farquhar, Marilyn G. Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin) |
title | Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin) |
title_full | Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin) |
title_fullStr | Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin) |
title_full_unstemmed | Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin) |
title_short | Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin) |
title_sort | gαs promotes eea1 endosome maturation and shuts down proliferative signaling through interaction with giv (girdin) |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510023/ https://www.ncbi.nlm.nih.gov/pubmed/23051738 http://dx.doi.org/10.1091/mbc.E12-02-0133 |
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