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

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 in...

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Bibliographic Details
Published in:The EMBO journal 2010-07, Vol.29 (14), p.2315-2328
Main Authors: Barda-Saad, Mira, Shirasu, Naoto, Pauker, Maor H, Hassan, Nirit, Perl, Orly, Balbo, Andrea, Yamaguchi, Hiroshi, Houtman, Jon C D, Appella, Ettore, Schuck, Peter, Samelson, Lawrence E
Format: Article
Language:English
Subjects:
actin polymerization
Actins - metabolism
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antigens
Cellular biology
EMBO19
EMBO37
Gene expression
Humans
Immune system
Jurkat Cells
Lymphocyte Activation
Lymphocytes
Molecular biology
Oncogene Proteins - genetics
Oncogene Proteins - metabolism
Phosphoproteins - genetics
Phosphoproteins - metabolism
Protein Binding
Proto-Oncogene Proteins c-vav - genetics
Proto-Oncogene Proteins c-vav - metabolism
Receptors, Antigen, T-Cell - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Signal transduction
Signal Transduction - physiology
signalling complexes
SLP-76
src Homology Domains
T-Lymphocytes - cytology
T-Lymphocytes - metabolism
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2010.133