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.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Pauker MH,Reicher B,Fried S,Perl O,Barda-Saad Mdoi
10.1128/MCB.01358-10subject
Has Abstractpub_date
2011-07-01 00:00:00pages
2653-66issue
13eissn
0270-7306issn
1098-5549pii
MCB.01358-10journal_volume
31pub_type
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