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Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum
EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Anky...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society for Biochemistry and Molecular Biology
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346308/ https://www.ncbi.nlm.nih.gov/pubmed/27802842 http://dx.doi.org/10.5483/BMBRep.2016.49.12.186 |
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author | Park, Soochul |
author_facet | Park, Soochul |
author_sort | Park, Soochul |
collection | PubMed |
description | EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis. Strikingly, ErbB2 did not localize to the cell surface following Anks1a knockdown in primary mammary tumor cells over-expressing ErbB2. Importantly, EphA2 was critical for stabilizing ErbB2 through complex formation, but its interaction with Anks1a also facilitated ErbB2 loading into COPII carriers. These findings suggest a novel role for Anks1a in the molecular pathogenesis of breast tumors and possibly other human diseases. |
format | Online Article Text |
id | pubmed-5346308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-53463082017-03-28 Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum Park, Soochul BMB Rep Perspective EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis. Strikingly, ErbB2 did not localize to the cell surface following Anks1a knockdown in primary mammary tumor cells over-expressing ErbB2. Importantly, EphA2 was critical for stabilizing ErbB2 through complex formation, but its interaction with Anks1a also facilitated ErbB2 loading into COPII carriers. These findings suggest a novel role for Anks1a in the molecular pathogenesis of breast tumors and possibly other human diseases. Korean Society for Biochemistry and Molecular Biology 2016 2016-12-31 /pmc/articles/PMC5346308/ /pubmed/27802842 http://dx.doi.org/10.5483/BMBRep.2016.49.12.186 Text en Copyright © 2016 by the The Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Perspective Park, Soochul Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum |
title | Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum |
title_full | Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum |
title_fullStr | Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum |
title_full_unstemmed | Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum |
title_short | Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum |
title_sort | defective anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346308/ https://www.ncbi.nlm.nih.gov/pubmed/27802842 http://dx.doi.org/10.5483/BMBRep.2016.49.12.186 |
work_keys_str_mv | AT parksoochul defectiveanks1adisruptstheexportofreceptortyrosinekinasesfromtheendoplasmicreticulum |