Epidermal loss of Gαq 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, Gαq and Gα11, activate one of the main GPCR...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5354386?pdf=render |
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| author | Colleen L Doçi Constantinos M Mikelis Juan Luis Callejas-Valera Karina K Hansen Alfredo A Molinolo Asuka Inoue Stefan Offermanns J Silvio Gutkind |
| author_facet | Colleen L Doçi Constantinos M Mikelis Juan Luis Callejas-Valera Karina K Hansen Alfredo A Molinolo Asuka Inoue Stefan Offermanns J Silvio Gutkind |
| author_sort | Colleen L Doçi |
| collection | DOAJ |
| 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, Gαq and Gα11, 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 Gα11 and Gαq from endothelial cells impairs the Rho-mediated formation of focal adherens junctions, suggesting that Gα11/q signaling may also play a significant role in cytoskeletal-mediated cellular responses in epithelial cells. Indeed, combined deletion of Gα11 and Gαq 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 Gαq-null keratinocytes under combined Gα11 deficiency. In fact, cells lacking Gα11/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 Gα11/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 Gα11/q signaling, implicating its upstream regulation as a potential therapeutic target in a host of pathologic conditions. |
| first_indexed | 2024-12-13T11:23:47Z |
| format | Article |
| id | doaj.art-df420c4435414d65b2c0651af441b2d3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T11:23:47Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-df420c4435414d65b2c0651af441b2d32022-12-21T23:48:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017369210.1371/journal.pone.0173692Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes.Colleen L DoçiConstantinos M MikelisJuan Luis Callejas-ValeraKarina K HansenAlfredo A MolinoloAsuka InoueStefan OffermannsJ Silvio GutkindG-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, Gαq and Gα11, 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 Gα11 and Gαq from endothelial cells impairs the Rho-mediated formation of focal adherens junctions, suggesting that Gα11/q signaling may also play a significant role in cytoskeletal-mediated cellular responses in epithelial cells. Indeed, combined deletion of Gα11 and Gαq 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 Gαq-null keratinocytes under combined Gα11 deficiency. In fact, cells lacking Gα11/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 Gα11/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 Gα11/q signaling, implicating its upstream regulation as a potential therapeutic target in a host of pathologic conditions.http://europepmc.org/articles/PMC5354386?pdf=render |
| spellingShingle | Colleen L Doçi Constantinos M Mikelis Juan Luis Callejas-Valera Karina K Hansen Alfredo A Molinolo Asuka Inoue Stefan Offermanns J Silvio Gutkind Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes. PLoS ONE |
| title | Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes. |
| title_full | Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes. |
| title_fullStr | Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes. |
| title_full_unstemmed | Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes. |
| title_short | Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes. |
| title_sort | epidermal loss of gαq confers a migratory and differentiation defect in keratinocytes |
| url | http://europepmc.org/articles/PMC5354386?pdf=render |
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