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

Jeffrey C. Nolz, Lucas P. Nacusi, Colin M. Segovis, Ricardo B. Medeiros, Jason S Mitchell, Yoji Shimizu, Daniel D. Billadeau

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1231-1244
Number of pages14
JournalJournal of Cell Biology
Volume182
Issue number6
DOIs
StatePublished - Sep 22 2008

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T-Cell Antigen Receptor
Integrins
Cluster Analysis
Immunological Synapses
Talin
Vinculin
Guanine Nucleotide Exchange Factors
Membranes
Guanosine
Protein-Tyrosine Kinases
Ligation
Tyrosine
Actins
Phosphorylation

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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.

In: Journal of Cell Biology, Vol. 182, No. 6, 22.09.2008, p. 1231-1244.

Research output: Contribution to journalArticle

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. In: Journal of Cell Biology. 2008 ; Vol. 182, No. 6. pp. 1231-1244.
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AU - Billadeau, Daniel D.

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