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GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration

RhoU is an atypical Rho family member with high homology to CDC42 but containing unique N- and C-terminal extensions. The mechanisms regulating RhoU activation, as well as its downstream effectors, are not fully characterized. We show that after epidermal growth factor (EGF) stimulation RhoU colocal...

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Detalles Bibliográficos
Autores principales: Zhang, Jin-San, Koenig, Alexander, Young, Charles, Billadeau, Daniel D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113775/
https://www.ncbi.nlm.nih.gov/pubmed/21508312
http://dx.doi.org/10.1091/mbc.E10-12-0969
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author Zhang, Jin-San
Koenig, Alexander
Young, Charles
Billadeau, Daniel D.
author_facet Zhang, Jin-San
Koenig, Alexander
Young, Charles
Billadeau, Daniel D.
author_sort Zhang, Jin-San
collection PubMed
description RhoU is an atypical Rho family member with high homology to CDC42 but containing unique N- and C-terminal extensions. The mechanisms regulating RhoU activation, as well as its downstream effectors, are not fully characterized. We show that after epidermal growth factor (EGF) stimulation RhoU colocalizes with EGF receptor (EGFR) on endosomes, which requires both its N- and C-terminal extension sequences. Moreover, RhoU physically associates with activated EGFR in a GRB2-dependent manner through specific proline-rich motifs within its N-terminus. Mutation of these proline-rich sequences or suppression of GRB2 by RNA interference abrogates the interaction of RhoU with activated EGFR, as well as EGF-stimulated RhoU GTP binding. In addition, RhoU is involved in EGFR-mediated signaling, leading to AP1 transcriptional activity and cell migration in pancreatic cancer cells, events that require its interaction with the Grb2–EGFR complex. Taken together, the data suggest a unique regulatory mechanism by which RhoU interaction with SH3 adaptor proteins might serve to integrate growth factor receptor signaling with RhoU activation.
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spelling pubmed-31137752011-08-30 GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration Zhang, Jin-San Koenig, Alexander Young, Charles Billadeau, Daniel D. Mol Biol Cell Articles RhoU is an atypical Rho family member with high homology to CDC42 but containing unique N- and C-terminal extensions. The mechanisms regulating RhoU activation, as well as its downstream effectors, are not fully characterized. We show that after epidermal growth factor (EGF) stimulation RhoU colocalizes with EGF receptor (EGFR) on endosomes, which requires both its N- and C-terminal extension sequences. Moreover, RhoU physically associates with activated EGFR in a GRB2-dependent manner through specific proline-rich motifs within its N-terminus. Mutation of these proline-rich sequences or suppression of GRB2 by RNA interference abrogates the interaction of RhoU with activated EGFR, as well as EGF-stimulated RhoU GTP binding. In addition, RhoU is involved in EGFR-mediated signaling, leading to AP1 transcriptional activity and cell migration in pancreatic cancer cells, events that require its interaction with the Grb2–EGFR complex. Taken together, the data suggest a unique regulatory mechanism by which RhoU interaction with SH3 adaptor proteins might serve to integrate growth factor receptor signaling with RhoU activation. The American Society for Cell Biology 2011-06-15 /pmc/articles/PMC3113775/ /pubmed/21508312 http://dx.doi.org/10.1091/mbc.E10-12-0969 Text en © 2011 Zhang 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
Zhang, Jin-San
Koenig, Alexander
Young, Charles
Billadeau, Daniel D.
GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration
title GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration
title_full GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration
title_fullStr GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration
title_full_unstemmed GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration
title_short GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration
title_sort grb2 couples rhou to epidermal growth factor receptor signaling and cell migration
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113775/
https://www.ncbi.nlm.nih.gov/pubmed/21508312
http://dx.doi.org/10.1091/mbc.E10-12-0969
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