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Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1

Stimulation by chemokines of integrin α4β1–dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correl...

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Autores principales: Dios-Esponera, Ana, Isern de Val, Soledad, Sevilla-Movilla, Silvia, García-Verdugo, Rosa, García-Bernal, David, Arellano-Sánchez, Nohemí, Cabañas, Carlos, Teixidó, Joaquin
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/PMC4569313/
https://www.ncbi.nlm.nih.gov/pubmed/26202465
http://dx.doi.org/10.1091/mbc.E14-07-1246
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author Dios-Esponera, Ana
Isern de Val, Soledad
Sevilla-Movilla, Silvia
García-Verdugo, Rosa
García-Bernal, David
Arellano-Sánchez, Nohemí
Cabañas, Carlos
Teixidó, Joaquin
author_facet Dios-Esponera, Ana
Isern de Val, Soledad
Sevilla-Movilla, Silvia
García-Verdugo, Rosa
García-Bernal, David
Arellano-Sánchez, Nohemí
Cabañas, Carlos
Teixidó, Joaquin
author_sort Dios-Esponera, Ana
collection PubMed
description Stimulation by chemokines of integrin α4β1–dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase–inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76–, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation.
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spelling pubmed-45693132015-11-30 Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1 Dios-Esponera, Ana Isern de Val, Soledad Sevilla-Movilla, Silvia García-Verdugo, Rosa García-Bernal, David Arellano-Sánchez, Nohemí Cabañas, Carlos Teixidó, Joaquin Mol Biol Cell Articles Stimulation by chemokines of integrin α4β1–dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase–inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76–, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. The American Society for Cell Biology 2015-09-15 /pmc/articles/PMC4569313/ /pubmed/26202465 http://dx.doi.org/10.1091/mbc.E14-07-1246 Text en © 2015 Dios-Esponera, Isern de Val, 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
Dios-Esponera, Ana
Isern de Val, Soledad
Sevilla-Movilla, Silvia
García-Verdugo, Rosa
García-Bernal, David
Arellano-Sánchez, Nohemí
Cabañas, Carlos
Teixidó, Joaquin
Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1
title Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1
title_full Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1
title_fullStr Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1
title_full_unstemmed Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1
title_short Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1
title_sort positive and negative regulation by slp-76/adap and pyk2 of chemokine-stimulated t-lymphocyte adhesion mediated by integrin α4β1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569313/
https://www.ncbi.nlm.nih.gov/pubmed/26202465
http://dx.doi.org/10.1091/mbc.E14-07-1246
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