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Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins
GIV/Girdin is a multimodular signal transducer and a bona fide metastasis-related protein. As a guanidine exchange factor (GEF), GIV modulates signals initiated by growth factors (chemical signals) by activating the G protein Gαi. Here we report that mechanical signals triggered by the extracellular...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666128/ https://www.ncbi.nlm.nih.gov/pubmed/26446841 http://dx.doi.org/10.1091/mbc.E15-07-0496 |
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author | Lopez-Sanchez, Inmaculada Kalogriopoulos, Nicholas Lo, I-Chung Kabir, Firooz Midde, Krishna K. Wang, Honghui Ghosh, Pradipta |
author_facet | Lopez-Sanchez, Inmaculada Kalogriopoulos, Nicholas Lo, I-Chung Kabir, Firooz Midde, Krishna K. Wang, Honghui Ghosh, Pradipta |
author_sort | Lopez-Sanchez, Inmaculada |
collection | PubMed |
description | GIV/Girdin is a multimodular signal transducer and a bona fide metastasis-related protein. As a guanidine exchange factor (GEF), GIV modulates signals initiated by growth factors (chemical signals) by activating the G protein Gαi. Here we report that mechanical signals triggered by the extracellular matrix (ECM) also converge on GIV-GEF via β1 integrins and that focal adhesions (FAs) serve as the major hubs for mechanochemical signaling via GIV. GIV interacts with focal adhesion kinase (FAK) and ligand-activated β1 integrins. Phosphorylation of GIV by FAK enhances PI3K-Akt signaling, the integrity of FAs, increases cell–ECM adhesion, and triggers ECM-induced cell motility. Activation of Gαi by GIV-GEF further potentiates FAK-GIV-PI3K-Akt signaling at the FAs. Spatially restricted signaling via tyrosine phosphorylated GIV at the FAs is enhanced during cancer metastasis. Thus GIV-GEF serves as a unifying platform for integration and amplification of adhesion (mechanical) and growth factor (chemical) signals during cancer progression. |
format | Online Article Text |
id | pubmed-4666128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-46661282016-02-16 Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins Lopez-Sanchez, Inmaculada Kalogriopoulos, Nicholas Lo, I-Chung Kabir, Firooz Midde, Krishna K. Wang, Honghui Ghosh, Pradipta Mol Biol Cell Brief Report GIV/Girdin is a multimodular signal transducer and a bona fide metastasis-related protein. As a guanidine exchange factor (GEF), GIV modulates signals initiated by growth factors (chemical signals) by activating the G protein Gαi. Here we report that mechanical signals triggered by the extracellular matrix (ECM) also converge on GIV-GEF via β1 integrins and that focal adhesions (FAs) serve as the major hubs for mechanochemical signaling via GIV. GIV interacts with focal adhesion kinase (FAK) and ligand-activated β1 integrins. Phosphorylation of GIV by FAK enhances PI3K-Akt signaling, the integrity of FAs, increases cell–ECM adhesion, and triggers ECM-induced cell motility. Activation of Gαi by GIV-GEF further potentiates FAK-GIV-PI3K-Akt signaling at the FAs. Spatially restricted signaling via tyrosine phosphorylated GIV at the FAs is enhanced during cancer metastasis. Thus GIV-GEF serves as a unifying platform for integration and amplification of adhesion (mechanical) and growth factor (chemical) signals during cancer progression. The American Society for Cell Biology 2015-12-01 /pmc/articles/PMC4666128/ /pubmed/26446841 http://dx.doi.org/10.1091/mbc.E15-07-0496 Text en © 2015 Lopez-Sanchez 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 for Cell Biology. |
spellingShingle | Brief Report Lopez-Sanchez, Inmaculada Kalogriopoulos, Nicholas Lo, I-Chung Kabir, Firooz Midde, Krishna K. Wang, Honghui Ghosh, Pradipta Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins |
title | Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins |
title_full | Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins |
title_fullStr | Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins |
title_full_unstemmed | Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins |
title_short | Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins |
title_sort | focal adhesions are foci for tyrosine-based signal transduction via giv/girdin and g proteins |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666128/ https://www.ncbi.nlm.nih.gov/pubmed/26446841 http://dx.doi.org/10.1091/mbc.E15-07-0496 |
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