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ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
The cellular events that precede myelination in the peripheral nervous system require rapid and dynamic morphological changes in the Schwann cell. These events are thought to be mainly controlled by axonal signals. But how signals on the axons are coordinately organized and transduced to promote pro...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315680/ https://www.ncbi.nlm.nih.gov/pubmed/18426980 http://dx.doi.org/10.1083/jcb.200709033 |
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author | Yamauchi, Junji Miyamoto, Yuki Chan, Jonah R. Tanoue, Akito |
author_facet | Yamauchi, Junji Miyamoto, Yuki Chan, Jonah R. Tanoue, Akito |
author_sort | Yamauchi, Junji |
collection | PubMed |
description | The cellular events that precede myelination in the peripheral nervous system require rapid and dynamic morphological changes in the Schwann cell. These events are thought to be mainly controlled by axonal signals. But how signals on the axons are coordinately organized and transduced to promote proliferation, migration, radial sorting, and myelination is unknown. We describe that the axonal signal neuregulin-1 (NRG1) controls Schwann cell migration via activation of the atypical Dock180-related guanine nucleotide exchange factor (GEF) Dock7 and subsequent activation of the Rho guanine triphosphatases (GTPases) Rac1 and Cdc42 and the downstream c-Jun N-terminal kinase. We show that the NRG1 receptor ErbB2 directly binds and activates Dock7 by phosphorylating Tyr-1118. Dock7 knockdown, or expression of Dock7 harboring the Tyr-1118–to–Phe mutation in Schwann cells, attenuates the effects of NRG1. Thus, Dock7 functions as an intracellular substrate for ErbB2 to promote Schwann cell migration. This provides an unanticipated mechanism through which ligand-dependent tyrosine phosphorylation can trigger the activation of Rho GTPase-GEFs of the Dock180 family. |
format | Text |
id | pubmed-2315680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-23156802008-10-21 ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration Yamauchi, Junji Miyamoto, Yuki Chan, Jonah R. Tanoue, Akito J Cell Biol Research Articles The cellular events that precede myelination in the peripheral nervous system require rapid and dynamic morphological changes in the Schwann cell. These events are thought to be mainly controlled by axonal signals. But how signals on the axons are coordinately organized and transduced to promote proliferation, migration, radial sorting, and myelination is unknown. We describe that the axonal signal neuregulin-1 (NRG1) controls Schwann cell migration via activation of the atypical Dock180-related guanine nucleotide exchange factor (GEF) Dock7 and subsequent activation of the Rho guanine triphosphatases (GTPases) Rac1 and Cdc42 and the downstream c-Jun N-terminal kinase. We show that the NRG1 receptor ErbB2 directly binds and activates Dock7 by phosphorylating Tyr-1118. Dock7 knockdown, or expression of Dock7 harboring the Tyr-1118–to–Phe mutation in Schwann cells, attenuates the effects of NRG1. Thus, Dock7 functions as an intracellular substrate for ErbB2 to promote Schwann cell migration. This provides an unanticipated mechanism through which ligand-dependent tyrosine phosphorylation can trigger the activation of Rho GTPase-GEFs of the Dock180 family. The Rockefeller University Press 2008-04-21 /pmc/articles/PMC2315680/ /pubmed/18426980 http://dx.doi.org/10.1083/jcb.200709033 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Yamauchi, Junji Miyamoto, Yuki Chan, Jonah R. Tanoue, Akito ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration |
title | ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration |
title_full | ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration |
title_fullStr | ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration |
title_full_unstemmed | ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration |
title_short | ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration |
title_sort | erbb2 directly activates the exchange factor dock7 to promote schwann cell migration |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315680/ https://www.ncbi.nlm.nih.gov/pubmed/18426980 http://dx.doi.org/10.1083/jcb.200709033 |
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