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

Mira Barda‐Saad, N Shirasu, M.H Pauker, N Hassan, O Perl, A Balbo, H Yamaguchi, J.C Houtman, E Appella, P Schuck, L.E Samelson

Research output: Contribution to journalArticlepeer-review


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 languageAmerican English
Pages (from-to)2315-2328
JournalThe EMBO Journal
Issue number14
StatePublished - 2010


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