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PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration
Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying MCP1-induced VSMC migration have not been understood. Here we identify the signaling pathway associated with MCP1-induced human aortic smooth...
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/PMC4678017/ https://www.ncbi.nlm.nih.gov/pubmed/26490115 http://dx.doi.org/10.1091/mbc.E15-08-0570 |
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author | Janjanam, Jagadeesh Chandaka, Giri Kumar Kotla, Sivareddy Rao, Gadiparthi N. |
author_facet | Janjanam, Jagadeesh Chandaka, Giri Kumar Kotla, Sivareddy Rao, Gadiparthi N. |
author_sort | Janjanam, Jagadeesh |
collection | PubMed |
description | Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying MCP1-induced VSMC migration have not been understood. Here we identify the signaling pathway associated with MCP1-induced human aortic smooth muscle cell (HASMC) migration. MCP1, a G protein–coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required for cell migration. In addition, the MCP1-induced cortactin phosphorylation is dependent on PLCβ3-mediated PKCδ activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, affecting G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Upstream, MCP1 activates CCR2 and Gαq/11 in a time-dependent manner, and down-regulation of their levels attenuates MCP1-induced PLCβ3 and PKCδ activation, cortactin phosphorylation, cortactin–WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. |
format | Online Article Text |
id | pubmed-4678017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-46780172016-03-01 PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration Janjanam, Jagadeesh Chandaka, Giri Kumar Kotla, Sivareddy Rao, Gadiparthi N. Mol Biol Cell Articles Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying MCP1-induced VSMC migration have not been understood. Here we identify the signaling pathway associated with MCP1-induced human aortic smooth muscle cell (HASMC) migration. MCP1, a G protein–coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required for cell migration. In addition, the MCP1-induced cortactin phosphorylation is dependent on PLCβ3-mediated PKCδ activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, affecting G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Upstream, MCP1 activates CCR2 and Gαq/11 in a time-dependent manner, and down-regulation of their levels attenuates MCP1-induced PLCβ3 and PKCδ activation, cortactin phosphorylation, cortactin–WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. The American Society for Cell Biology 2015-12-15 /pmc/articles/PMC4678017/ /pubmed/26490115 http://dx.doi.org/10.1091/mbc.E15-08-0570 Text en © 2015 Janjanam 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 | Articles Janjanam, Jagadeesh Chandaka, Giri Kumar Kotla, Sivareddy Rao, Gadiparthi N. PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration |
title | PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration |
title_full | PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration |
title_fullStr | PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration |
title_full_unstemmed | PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration |
title_short | PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration |
title_sort | plcβ3 mediates cortactin interaction with wave2 in mcp1-induced actin polymerization and cell migration |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678017/ https://www.ncbi.nlm.nih.gov/pubmed/26490115 http://dx.doi.org/10.1091/mbc.E15-08-0570 |
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