Functional cooperation between the proteins Nck and ADAP is fundamental for actin reorganization

Maor H. Pauker, Barak Reicher, Sophie Fried, Orly Perl, Mira Barda-Saad

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

T cell antigen receptor (TCR) activation triggers profound changes in the actin cytoskeleton. In addition to controlling cellular shape and polarity, this process regulates vital T cell responses, such as T cell adhesion, motility, and proliferation. These depend on the recruitment of the signaling proteins Nck and Wiskott-Aldrich syndrome protein (WASp) to the site of TCR activation and on the functional properties of the adapter proteins linker for activation of T cells (LAT) and SH2-domain-containing leukocyte protein of 76 kDa (SLP76). We now demonstrate that Nck is necessary but insufficient for the recruitment of WASp. We show that two pathways lead to SLP76-dependent actin rearrangement. One requires the SLP76 acidic domain, crucial to association with the Nck SH2 domain, and another requires the SLP76 SH2 domain, essential for interaction with the adhesion- and degranulation-promoting adapter protein ADAP. Functional cooperation between Nck and ADAP mediates SLP76-WASp interactions and actin rearrangement. We also reveal the molecular mechanism linking ADAP to actin reorganization.

Original languageEnglish
Pages (from-to)2653-2666
Number of pages14
JournalMolecular and Cellular Biology
Volume31
Issue number13
DOIs
StatePublished - Jul 2011

Bibliographical note

This research was funded by the Israeli Ministry of Health through the Office of the Chief Scientist and by the Israel Science Foundation (grants 1659/08 and 971/08).

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