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Epidermal loss of Gα(q) confers a migratory and differentiation defect in keratinocytes

G-protein coupled receptors (GPCRs), which activate heterotrimeric G proteins, are an essential class of transmembrane receptors that are responsible for a myriad of signaling events in normal and pathologic conditions. Two members of the G protein family, Gα(q) and Gα(11), activate one of the main...

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Autores principales: Doçi, Colleen L., Mikelis, Constantinos M., Callejas-Valera, Juan Luis, Hansen, Karina K., Molinolo, Alfredo A., Inoue, Asuka, Offermanns, Stefan, Gutkind, J. Silvio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354386/
https://www.ncbi.nlm.nih.gov/pubmed/28301547
http://dx.doi.org/10.1371/journal.pone.0173692
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author Doçi, Colleen L.
Mikelis, Constantinos M.
Callejas-Valera, Juan Luis
Hansen, Karina K.
Molinolo, Alfredo A.
Inoue, Asuka
Offermanns, Stefan
Gutkind, J. Silvio
author_facet Doçi, Colleen L.
Mikelis, Constantinos M.
Callejas-Valera, Juan Luis
Hansen, Karina K.
Molinolo, Alfredo A.
Inoue, Asuka
Offermanns, Stefan
Gutkind, J. Silvio
author_sort Doçi, Colleen L.
collection PubMed
description G-protein coupled receptors (GPCRs), which activate heterotrimeric G proteins, are an essential class of transmembrane receptors that are responsible for a myriad of signaling events in normal and pathologic conditions. Two members of the G protein family, Gα(q) and Gα(11), activate one of the main GPCR pathways and function as oncogenes by integrating mitogen-stimulated signaling cascades that are active under malignant conditions. Recently, it has been shown that targeted deletion of Gα(11) and Gα(q) from endothelial cells impairs the Rho-mediated formation of focal adherens junctions, suggesting that Gα(11/q) signaling may also play a significant role in cytoskeletal-mediated cellular responses in epithelial cells. Indeed, combined deletion of Gα(11) and Gα(q) confers a significant migratory defect in keratinocytes that delays cutaneous wound healing in an in vivo setting. This delay can be attributed to a defect during the reepithelialization phase due to significantly attenuated migratory capacity of Gα(q)-null keratinocytes under combined Gα(11) deficiency. In fact, cells lacking Gα(11/q) demonstrate a severely reduced ability to respond to mitogenic and migratory signals in the microenvironment, leading to inappropriate and premature terminal differentiation. These results suggest that Gα(11/q) signaling pathways may be critical for integrating mitogenic signals and cytoskeletal function to achieve normal physiological responses. Emergence of a malignant phenotype may therefore arise from both under- and overexpression of Gα(11/q) signaling, implicating its upstream regulation as a potential therapeutic target in a host of pathologic conditions.
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spelling pubmed-53543862017-04-06 Epidermal loss of Gα(q) confers a migratory and differentiation defect in keratinocytes Doçi, Colleen L. Mikelis, Constantinos M. Callejas-Valera, Juan Luis Hansen, Karina K. Molinolo, Alfredo A. Inoue, Asuka Offermanns, Stefan Gutkind, J. Silvio PLoS One Research Article G-protein coupled receptors (GPCRs), which activate heterotrimeric G proteins, are an essential class of transmembrane receptors that are responsible for a myriad of signaling events in normal and pathologic conditions. Two members of the G protein family, Gα(q) and Gα(11), activate one of the main GPCR pathways and function as oncogenes by integrating mitogen-stimulated signaling cascades that are active under malignant conditions. Recently, it has been shown that targeted deletion of Gα(11) and Gα(q) from endothelial cells impairs the Rho-mediated formation of focal adherens junctions, suggesting that Gα(11/q) signaling may also play a significant role in cytoskeletal-mediated cellular responses in epithelial cells. Indeed, combined deletion of Gα(11) and Gα(q) confers a significant migratory defect in keratinocytes that delays cutaneous wound healing in an in vivo setting. This delay can be attributed to a defect during the reepithelialization phase due to significantly attenuated migratory capacity of Gα(q)-null keratinocytes under combined Gα(11) deficiency. In fact, cells lacking Gα(11/q) demonstrate a severely reduced ability to respond to mitogenic and migratory signals in the microenvironment, leading to inappropriate and premature terminal differentiation. These results suggest that Gα(11/q) signaling pathways may be critical for integrating mitogenic signals and cytoskeletal function to achieve normal physiological responses. Emergence of a malignant phenotype may therefore arise from both under- and overexpression of Gα(11/q) signaling, implicating its upstream regulation as a potential therapeutic target in a host of pathologic conditions. Public Library of Science 2017-03-16 /pmc/articles/PMC5354386/ /pubmed/28301547 http://dx.doi.org/10.1371/journal.pone.0173692 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Doçi, Colleen L.
Mikelis, Constantinos M.
Callejas-Valera, Juan Luis
Hansen, Karina K.
Molinolo, Alfredo A.
Inoue, Asuka
Offermanns, Stefan
Gutkind, J. Silvio
Epidermal loss of Gα(q) confers a migratory and differentiation defect in keratinocytes
title Epidermal loss of Gα(q) confers a migratory and differentiation defect in keratinocytes
title_full Epidermal loss of Gα(q) confers a migratory and differentiation defect in keratinocytes
title_fullStr Epidermal loss of Gα(q) confers a migratory and differentiation defect in keratinocytes
title_full_unstemmed Epidermal loss of Gα(q) confers a migratory and differentiation defect in keratinocytes
title_short Epidermal loss of Gα(q) confers a migratory and differentiation defect in keratinocytes
title_sort epidermal loss of gα(q) confers a migratory and differentiation defect in keratinocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354386/
https://www.ncbi.nlm.nih.gov/pubmed/28301547
http://dx.doi.org/10.1371/journal.pone.0173692
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