TY - JOUR
T1 - Functional cooperation between the proteins Nck and ADAP is fundamental for actin reorganization
AU - Pauker, Maor H.
AU - Reicher, Barak
AU - Fried, Sophie
AU - Perl, Orly
AU - Barda-Saad, Mira
N1 - 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).
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79959396065&partnerID=8YFLogxK
U2 - 10.1128/MCB.01358-10
DO - 10.1128/MCB.01358-10
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C2 - 21536650
AN - SCOPUS:79959396065
SN - 0270-7306
VL - 31
SP - 2653
EP - 2666
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 13
ER -