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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...

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Autores principales: Lopez-Sanchez, Inmaculada, Kalogriopoulos, Nicholas, Lo, I-Chung, Kabir, Firooz, Midde, Krishna K., Wang, Honghui, Ghosh, Pradipta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
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.
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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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