Cooperative interactions at the SLP-76 complex are critical for actin polymerization

Mira Barda-Saad; Naoto Shirasu; Maor H. Pauker; Nirit Hassan; Orly Perl; Andrea Balbo; Hiroshi Yamaguchi; Jon C.D. Houtman; Ettore Appella; Peter Schuck; Lawrence E. Samelson

doi:10.1038/emboj.2010.133

Cooperative interactions at the SLP-76 complex are critical for actin polymerization

Mira Barda-Saad, Naoto Shirasu, Maor H. Pauker, Nirit Hassan, Orly Perl, Andrea Balbo, Hiroshi Yamaguchi, Jon C.D. Houtman, Ettore Appella, Peter Schuck, Lawrence E. Samelson

The Mina and Everard Goodman Faculty of Life Sciences

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex. Our data reveal that this complex can contain one SLP-76 molecule, two Nck and two VAV1 molecules. A direct interaction between Nck and VAV1 is mediated by binding between the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain. Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation.

Original language	English
Pages (from-to)	2315-2328
Number of pages	14
Journal	EMBO Journal
Volume	29
Issue number	14
DOIs	https://doi.org/10.1038/emboj.2010.133
State	Published - 21 Jul 2010

Keywords

SLP-76
actin polymerization
lymphocyte activation
signalling complexes

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10.1038/emboj.2010.133

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title = "Cooperative interactions at the SLP-76 complex are critical for actin polymerization",

abstract = "T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex. Our data reveal that this complex can contain one SLP-76 molecule, two Nck and two VAV1 molecules. A direct interaction between Nck and VAV1 is mediated by binding between the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain. Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation.",

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AU - Barda-Saad, Mira

AU - Shirasu, Naoto

AU - Pauker, Maor H.

AU - Hassan, Nirit

AU - Perl, Orly

AU - Balbo, Andrea

AU - Yamaguchi, Hiroshi

AU - Houtman, Jon C.D.

AU - Appella, Ettore

AU - Schuck, Peter

AU - Samelson, Lawrence E.

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AB - T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex. Our data reveal that this complex can contain one SLP-76 molecule, two Nck and two VAV1 molecules. A direct interaction between Nck and VAV1 is mediated by binding between the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain. Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation.

KW - SLP-76

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KW - lymphocyte activation

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Cooperative interactions at the SLP-76 complex are critical for actin polymerization

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Keywords

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