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A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics
Integrin adhesion complexes regulate cytoskeletal dynamics during cell migration. Adhesion activates phosphorylation of integrin-associated signaling proteins, including Cas (p130Cas, BCAR1), by Src-family kinases. Cas regulates leading-edge protrusion and migration in cooperation with its binding p...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266394/ https://www.ncbi.nlm.nih.gov/pubmed/34169835 http://dx.doi.org/10.7554/eLife.67078 |
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author | Steenkiste, Elizabeth M Berndt, Jason D Pilling, Carissa Simpkins, Christopher Cooper, Jonathan A |
author_facet | Steenkiste, Elizabeth M Berndt, Jason D Pilling, Carissa Simpkins, Christopher Cooper, Jonathan A |
author_sort | Steenkiste, Elizabeth M |
collection | PubMed |
description | Integrin adhesion complexes regulate cytoskeletal dynamics during cell migration. Adhesion activates phosphorylation of integrin-associated signaling proteins, including Cas (p130Cas, BCAR1), by Src-family kinases. Cas regulates leading-edge protrusion and migration in cooperation with its binding partner, BCAR3. However, it has been unclear how Cas and BCAR3 cooperate. Here, using normal epithelial cells, we find that BCAR3 localization to integrin adhesions requires Cas. In return, Cas phosphorylation, as well as lamellipodia dynamics and cell migration, requires BCAR3. These functions require the BCAR3 SH2 domain and a specific phosphorylation site, Tyr 117, that is also required for BCAR3 downregulation by the ubiquitin-proteasome system. These findings place BCAR3 in a co-regulatory positive-feedback circuit with Cas, with BCAR3 requiring Cas for localization and Cas requiring BCAR3 for activation and downstream signaling. The use of a single phosphorylation site in BCAR3 for activation and degradation ensures reliable negative feedback by the ubiquitin-proteasome system. |
format | Online Article Text |
id | pubmed-8266394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-82663942021-07-12 A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics Steenkiste, Elizabeth M Berndt, Jason D Pilling, Carissa Simpkins, Christopher Cooper, Jonathan A eLife Cell Biology Integrin adhesion complexes regulate cytoskeletal dynamics during cell migration. Adhesion activates phosphorylation of integrin-associated signaling proteins, including Cas (p130Cas, BCAR1), by Src-family kinases. Cas regulates leading-edge protrusion and migration in cooperation with its binding partner, BCAR3. However, it has been unclear how Cas and BCAR3 cooperate. Here, using normal epithelial cells, we find that BCAR3 localization to integrin adhesions requires Cas. In return, Cas phosphorylation, as well as lamellipodia dynamics and cell migration, requires BCAR3. These functions require the BCAR3 SH2 domain and a specific phosphorylation site, Tyr 117, that is also required for BCAR3 downregulation by the ubiquitin-proteasome system. These findings place BCAR3 in a co-regulatory positive-feedback circuit with Cas, with BCAR3 requiring Cas for localization and Cas requiring BCAR3 for activation and downstream signaling. The use of a single phosphorylation site in BCAR3 for activation and degradation ensures reliable negative feedback by the ubiquitin-proteasome system. eLife Sciences Publications, Ltd 2021-06-25 /pmc/articles/PMC8266394/ /pubmed/34169835 http://dx.doi.org/10.7554/eLife.67078 Text en © 2021, Steenkiste et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Steenkiste, Elizabeth M Berndt, Jason D Pilling, Carissa Simpkins, Christopher Cooper, Jonathan A A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics |
title | A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics |
title_full | A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics |
title_fullStr | A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics |
title_full_unstemmed | A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics |
title_short | A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics |
title_sort | cas-bcar3 co-regulatory circuit controls lamellipodia dynamics |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266394/ https://www.ncbi.nlm.nih.gov/pubmed/34169835 http://dx.doi.org/10.7554/eLife.67078 |
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