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The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL–C3G-mediated activation of Rap1

WAVE2 regulates T cell receptor (TCR)–stimulated actin cytoskeletal dynamics leading to both integrin clustering and affinity maturation. Although WAVE2 mediates integrin affinity maturation by recruiting vinculin and talin to the immunological synapse in an Arp2/3-dependent manner, the mechanism by...

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Detalles Bibliográficos
Autores principales: Nolz, Jeffrey C., Nacusi, Lucas P., Segovis, Colin M., Medeiros, Ricardo B., Mitchell, Jason S., Shimizu, Yoji, Billadeau, Daniel D.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542481/
https://www.ncbi.nlm.nih.gov/pubmed/18809728
http://dx.doi.org/10.1083/jcb.200801121
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author Nolz, Jeffrey C.
Nacusi, Lucas P.
Segovis, Colin M.
Medeiros, Ricardo B.
Mitchell, Jason S.
Shimizu, Yoji
Billadeau, Daniel D.
author_facet Nolz, Jeffrey C.
Nacusi, Lucas P.
Segovis, Colin M.
Medeiros, Ricardo B.
Mitchell, Jason S.
Shimizu, Yoji
Billadeau, Daniel D.
author_sort Nolz, Jeffrey C.
collection PubMed
description WAVE2 regulates T cell receptor (TCR)–stimulated actin cytoskeletal dynamics leading to both integrin clustering and affinity maturation. Although WAVE2 mediates integrin affinity maturation by recruiting vinculin and talin to the immunological synapse in an Arp2/3-dependent manner, the mechanism by which it regulates integrin clustering is unclear. We show that the Abl tyrosine kinase associates with the WAVE2 complex and TCR ligation induces WAVE2-dependent membrane recruitment of Abl. Furthermore, we show that WAVE2 regulates TCR-mediated activation of the integrin regulatory guanosine triphosphatase Rap1 via the recruitment and activation of the CrkL–C3G exchange complex. Moreover, we demonstrate that although Abl does not regulate the recruitment of CrkL–C3G into the membrane, it does affect the tyrosine phosphorylation of C3G, which is required for its guanine nucleotide exchange factor activity toward Rap1. This signaling node regulates not only TCR-stimulated integrin clustering but also affinity maturation. These findings identify a previously unknown mechanism by which the WAVE2 complex regulates TCR signaling to Rap1 and integrin activation.
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spelling pubmed-25424812009-03-22 The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL–C3G-mediated activation of Rap1 Nolz, Jeffrey C. Nacusi, Lucas P. Segovis, Colin M. Medeiros, Ricardo B. Mitchell, Jason S. Shimizu, Yoji Billadeau, Daniel D. J Cell Biol Research Articles WAVE2 regulates T cell receptor (TCR)–stimulated actin cytoskeletal dynamics leading to both integrin clustering and affinity maturation. Although WAVE2 mediates integrin affinity maturation by recruiting vinculin and talin to the immunological synapse in an Arp2/3-dependent manner, the mechanism by which it regulates integrin clustering is unclear. We show that the Abl tyrosine kinase associates with the WAVE2 complex and TCR ligation induces WAVE2-dependent membrane recruitment of Abl. Furthermore, we show that WAVE2 regulates TCR-mediated activation of the integrin regulatory guanosine triphosphatase Rap1 via the recruitment and activation of the CrkL–C3G exchange complex. Moreover, we demonstrate that although Abl does not regulate the recruitment of CrkL–C3G into the membrane, it does affect the tyrosine phosphorylation of C3G, which is required for its guanine nucleotide exchange factor activity toward Rap1. This signaling node regulates not only TCR-stimulated integrin clustering but also affinity maturation. These findings identify a previously unknown mechanism by which the WAVE2 complex regulates TCR signaling to Rap1 and integrin activation. The Rockefeller University Press 2008-09-22 /pmc/articles/PMC2542481/ /pubmed/18809728 http://dx.doi.org/10.1083/jcb.200801121 Text en © 2008 Nolz et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Nolz, Jeffrey C.
Nacusi, Lucas P.
Segovis, Colin M.
Medeiros, Ricardo B.
Mitchell, Jason S.
Shimizu, Yoji
Billadeau, Daniel D.
The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL–C3G-mediated activation of Rap1
title The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL–C3G-mediated activation of Rap1
title_full The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL–C3G-mediated activation of Rap1
title_fullStr The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL–C3G-mediated activation of Rap1
title_full_unstemmed The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL–C3G-mediated activation of Rap1
title_short The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL–C3G-mediated activation of Rap1
title_sort wave2 complex regulates t cell receptor signaling to integrins via abl- and crkl–c3g-mediated activation of rap1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542481/
https://www.ncbi.nlm.nih.gov/pubmed/18809728
http://dx.doi.org/10.1083/jcb.200801121
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