TY - JOUR
T1 - DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-θ and LFA-1, in T cells
AU - Sanui, Terukazu
AU - Inayoshi, Ayumi
AU - Noda, Mayuko
AU - Iwata, Eiko
AU - Oike, Masahiro
AU - Sasazuki, Takehiko
AU - Fukui, Yoshinori
N1 - Funding Information:
We thank M.M. Davis for 2B4 TCRαβ Tg mice and CH27 cells, and T. Saito for A2B4. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - DOCK2 is a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City which are known to regulate actin cytoskeleton. DOCK2 is critical for lymphocyte migration, yet the role of DOCK2 in TCR signaling remains unclear. We show here that DOCK2 is essential for TCR-mediated Rac activation and immunological synapse formation. In DOCK2-deficient T cells, antigen-induced translocation of TCR and lipid rafts, but not PKC-θ and LFA-1, to the APC interface was severely impaired, resulting in a significant reduction of antigen-specific T cell proliferation. In addition, we found that the efficacy of both positive and negative selection was reduced in DOCK2-deficient mice. These results suggest that DOCK2 regulates T cell responsiveness through remodeling of actin cytoskeleton via Rac activation.
AB - DOCK2 is a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City which are known to regulate actin cytoskeleton. DOCK2 is critical for lymphocyte migration, yet the role of DOCK2 in TCR signaling remains unclear. We show here that DOCK2 is essential for TCR-mediated Rac activation and immunological synapse formation. In DOCK2-deficient T cells, antigen-induced translocation of TCR and lipid rafts, but not PKC-θ and LFA-1, to the APC interface was severely impaired, resulting in a significant reduction of antigen-specific T cell proliferation. In addition, we found that the efficacy of both positive and negative selection was reduced in DOCK2-deficient mice. These results suggest that DOCK2 regulates T cell responsiveness through remodeling of actin cytoskeleton via Rac activation.
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U2 - 10.1016/S1074-7613(03)00169-9
DO - 10.1016/S1074-7613(03)00169-9
M3 - Article
C2 - 12871644
AN - SCOPUS:0038445857
SN - 1074-7613
VL - 19
SP - 119
EP - 129
JO - Immunity
JF - Immunity
IS - 1
ER -
