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

Research output: Contribution to journalArticlepeer-review

92 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 languageEnglish
Pages (from-to)2315-2328
Number of pages14
JournalEMBO Journal
Volume29
Issue number14
DOIs
StatePublished - 21 Jul 2010

Funding

FundersFunder number
National Cancer InstituteZIABC010304
National Institute of Biomedical Imaging and BioengineeringZICEB000008

    Keywords

    • SLP-76
    • actin polymerization
    • lymphocyte activation
    • signalling complexes

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