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.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism*
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Humans
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Jurkat Cells
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Lymphocyte Activation
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein Binding
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Proto-Oncogene Proteins c-vav / genetics
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Proto-Oncogene Proteins c-vav / metabolism*
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Receptors, Antigen, T-Cell / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology*
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T-Lymphocytes / cytology
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T-Lymphocytes / metabolism
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src Homology Domains
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Nck protein
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Oncogene Proteins
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Phosphoproteins
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Proto-Oncogene Proteins c-vav
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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SLP-76 signal Transducing adaptor proteins
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VAV1 protein, human