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A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src
Tumor cell migration is supported in part by the cyclic formation and disassembly of focal adhesions (FAs); however, the mechanisms that regulate this process are not fully defined. The large guanosine 5′-triphosphatase dynamin (Dyn) plays an important role in FA dynamics and is activated by tyrosin...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084675/ https://www.ncbi.nlm.nih.gov/pubmed/21411625 http://dx.doi.org/10.1091/mbc.E10-09-0785 |
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author | Wang, Yu Cao, Hong Chen, Jing McNiven, Mark A. |
author_facet | Wang, Yu Cao, Hong Chen, Jing McNiven, Mark A. |
author_sort | Wang, Yu |
collection | PubMed |
description | Tumor cell migration is supported in part by the cyclic formation and disassembly of focal adhesions (FAs); however, the mechanisms that regulate this process are not fully defined. The large guanosine 5′-triphosphatase dynamin (Dyn) plays an important role in FA dynamics and is activated by tyrosine phosphorylation. Using a novel antibody specific to phospho-dynamin (pDyn–Tyr-231), we found that Dyn2 is phosphorylated at FAs by Src kinase and is recruited to FAs by a direct interaction with the 4.1/ezrin/radizin/moesin domain of focal adhesion kinase (FAK), which functions as an adaptor between Src and Dyn2 to facilitate Dyn2 phosphorylation. This Src–FAK–Dyn2 trimeric complex is essential for FA turnover, as mutants disrupting the formation of this complex inhibit FA disassembly. Importantly, phosphoactivated Dyn2 promotes FA turnover by mediating the endocytosis of integrins in a clathrin-dependent manner. This study defines a novel mechanism of how Dyn2 functions as a downstream effector of FAK–Src signaling in turning over FAs. |
format | Text |
id | pubmed-3084675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30846752011-07-16 A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src Wang, Yu Cao, Hong Chen, Jing McNiven, Mark A. Mol Biol Cell Articles Tumor cell migration is supported in part by the cyclic formation and disassembly of focal adhesions (FAs); however, the mechanisms that regulate this process are not fully defined. The large guanosine 5′-triphosphatase dynamin (Dyn) plays an important role in FA dynamics and is activated by tyrosine phosphorylation. Using a novel antibody specific to phospho-dynamin (pDyn–Tyr-231), we found that Dyn2 is phosphorylated at FAs by Src kinase and is recruited to FAs by a direct interaction with the 4.1/ezrin/radizin/moesin domain of focal adhesion kinase (FAK), which functions as an adaptor between Src and Dyn2 to facilitate Dyn2 phosphorylation. This Src–FAK–Dyn2 trimeric complex is essential for FA turnover, as mutants disrupting the formation of this complex inhibit FA disassembly. Importantly, phosphoactivated Dyn2 promotes FA turnover by mediating the endocytosis of integrins in a clathrin-dependent manner. This study defines a novel mechanism of how Dyn2 functions as a downstream effector of FAK–Src signaling in turning over FAs. The American Society for Cell Biology 2011-05-01 /pmc/articles/PMC3084675/ /pubmed/21411625 http://dx.doi.org/10.1091/mbc.E10-09-0785 Text en © 2011 Wang 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 of Cell Biology. |
spellingShingle | Articles Wang, Yu Cao, Hong Chen, Jing McNiven, Mark A. A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src |
title | A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src |
title_full | A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src |
title_fullStr | A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src |
title_full_unstemmed | A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src |
title_short | A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src |
title_sort | direct interaction between the large gtpase dynamin-2 and fak regulates focal adhesion dynamics in response to active src |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084675/ https://www.ncbi.nlm.nih.gov/pubmed/21411625 http://dx.doi.org/10.1091/mbc.E10-09-0785 |
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