Endogenous RhoG Is Rapidly Activated after Epidermal Growth Factor Stimulation through Multiple Guanine-Nucleotide Exchange Factors

RhoG is a member of the Rac-like subgroup of Rho GTPases and has been linked to a variety of different cellular functions. Nevertheless, many aspects of RhoG upstream and downstream signaling remain unclear; in particular, few extracellular stimuli that modulate RhoG activity have been identified. H...

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Autores principales: Samson, Thomas, Welch, Christopher, Monaghan-Benson, Elizabeth, Hahn, Klaus M., Burridge, Keith
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861620/
https://www.ncbi.nlm.nih.gov/pubmed/20237158
http://dx.doi.org/10.1091/mbc.E09-09-0809
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author Samson, Thomas
Welch, Christopher
Monaghan-Benson, Elizabeth
Hahn, Klaus M.
Burridge, Keith
author_facet Samson, Thomas
Welch, Christopher
Monaghan-Benson, Elizabeth
Hahn, Klaus M.
Burridge, Keith
author_sort Samson, Thomas
collection PubMed
description RhoG is a member of the Rac-like subgroup of Rho GTPases and has been linked to a variety of different cellular functions. Nevertheless, many aspects of RhoG upstream and downstream signaling remain unclear; in particular, few extracellular stimuli that modulate RhoG activity have been identified. Here, we describe that stimulation of epithelial cells with epidermal growth factor leads to strong and rapid activation of RhoG. Importantly, this rapid activation was not observed with other growth factors tested. The kinetics of RhoG activation after epidermal growth factor (EGF) stimulation parallel the previously described Rac1 activation. However, we show that both GTPases are activated independently of one another. Kinase inhibition studies indicate that the rapid activation of RhoG and Rac1 after EGF treatment requires the activity of the EGF receptor kinase, but neither phosphatidylinositol 3-kinase nor Src kinases. By using nucleotide-free RhoG pull-down assays and small interfering RNA-mediated knockdown studies, we further show that guanine-nucleotide exchange factors (GEFs) of the Vav family mediate EGF-induced rapid activation of RhoG. In addition, we found that in certain cell types the recently described RhoG GEF PLEKHG6 can also contribute to the rapid activation of RhoG after EGF stimulation. Finally, we present results that show that RhoG has functions in EGF-stimulated cell migration and in regulating EGF receptor internalization.
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spelling pubmed-28616202010-07-16 Endogenous RhoG Is Rapidly Activated after Epidermal Growth Factor Stimulation through Multiple Guanine-Nucleotide Exchange Factors Samson, Thomas Welch, Christopher Monaghan-Benson, Elizabeth Hahn, Klaus M. Burridge, Keith Mol Biol Cell Articles RhoG is a member of the Rac-like subgroup of Rho GTPases and has been linked to a variety of different cellular functions. Nevertheless, many aspects of RhoG upstream and downstream signaling remain unclear; in particular, few extracellular stimuli that modulate RhoG activity have been identified. Here, we describe that stimulation of epithelial cells with epidermal growth factor leads to strong and rapid activation of RhoG. Importantly, this rapid activation was not observed with other growth factors tested. The kinetics of RhoG activation after epidermal growth factor (EGF) stimulation parallel the previously described Rac1 activation. However, we show that both GTPases are activated independently of one another. Kinase inhibition studies indicate that the rapid activation of RhoG and Rac1 after EGF treatment requires the activity of the EGF receptor kinase, but neither phosphatidylinositol 3-kinase nor Src kinases. By using nucleotide-free RhoG pull-down assays and small interfering RNA-mediated knockdown studies, we further show that guanine-nucleotide exchange factors (GEFs) of the Vav family mediate EGF-induced rapid activation of RhoG. In addition, we found that in certain cell types the recently described RhoG GEF PLEKHG6 can also contribute to the rapid activation of RhoG after EGF stimulation. Finally, we present results that show that RhoG has functions in EGF-stimulated cell migration and in regulating EGF receptor internalization. The American Society for Cell Biology 2010-05-01 /pmc/articles/PMC2861620/ /pubmed/20237158 http://dx.doi.org/10.1091/mbc.E09-09-0809 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Samson, Thomas
Welch, Christopher
Monaghan-Benson, Elizabeth
Hahn, Klaus M.
Burridge, Keith
Endogenous RhoG Is Rapidly Activated after Epidermal Growth Factor Stimulation through Multiple Guanine-Nucleotide Exchange Factors
title Endogenous RhoG Is Rapidly Activated after Epidermal Growth Factor Stimulation through Multiple Guanine-Nucleotide Exchange Factors
title_full Endogenous RhoG Is Rapidly Activated after Epidermal Growth Factor Stimulation through Multiple Guanine-Nucleotide Exchange Factors
title_fullStr Endogenous RhoG Is Rapidly Activated after Epidermal Growth Factor Stimulation through Multiple Guanine-Nucleotide Exchange Factors
title_full_unstemmed Endogenous RhoG Is Rapidly Activated after Epidermal Growth Factor Stimulation through Multiple Guanine-Nucleotide Exchange Factors
title_short Endogenous RhoG Is Rapidly Activated after Epidermal Growth Factor Stimulation through Multiple Guanine-Nucleotide Exchange Factors
title_sort endogenous rhog is rapidly activated after epidermal growth factor stimulation through multiple guanine-nucleotide exchange factors
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861620/
https://www.ncbi.nlm.nih.gov/pubmed/20237158
http://dx.doi.org/10.1091/mbc.E09-09-0809
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