TY - JOUR
T1 - Suppression of thymic development by the dominant-negative form of Gads
AU - Kikuchi, Kazu
AU - Kawasaki, Yoshitada
AU - Ishii, Naoto
AU - Sasaki, Yoshiteru
AU - Asao, Hironobu
AU - Takeshita, Toshikazu
AU - Miyoshi, Ichiro
AU - Kasai, Noriyuki
AU - Sugamura, Kazuo
PY - 2001
Y1 - 2001
N2 - Gads, a hematopoietic-lineage-specific Grb2 family member, is involved in the signaling mediated by the TCR through its interactions with SLP-76 and LAT. Here, we generated transgenic mice expressing Grf40-dSH2, an SH2-deleted dominant-negative form of Gads, which is driven by the lck proximal promoter. The total number of thymocytes was profoundly reduced in the transgenic mice, whereas in the double-negative (CD4-CD8-) thymocyte subset, in particular the CD25+CD44- pre-T cell population, it was significantly increased. However, CD5 expression, which is mediated by pre-TCR stimulation, was significantly suppressed on the CD4-CD8- thymocytes of the transgenic mice. Furthermore, the SLP-76-dependent signaling was markedly suppressed as well. These data suggest that Gads plays an important role in the pre-TCR as well as TCR signaling in thymocytes.
AB - Gads, a hematopoietic-lineage-specific Grb2 family member, is involved in the signaling mediated by the TCR through its interactions with SLP-76 and LAT. Here, we generated transgenic mice expressing Grf40-dSH2, an SH2-deleted dominant-negative form of Gads, which is driven by the lck proximal promoter. The total number of thymocytes was profoundly reduced in the transgenic mice, whereas in the double-negative (CD4-CD8-) thymocyte subset, in particular the CD25+CD44- pre-T cell population, it was significantly increased. However, CD5 expression, which is mediated by pre-TCR stimulation, was significantly suppressed on the CD4-CD8- thymocytes of the transgenic mice. Furthermore, the SLP-76-dependent signaling was markedly suppressed as well. These data suggest that Gads plays an important role in the pre-TCR as well as TCR signaling in thymocytes.
KW - Grb2 family
KW - LAT
KW - Pre-TCR signaling
KW - SLP-76
KW - TCR signaling
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U2 - 10.1093/intimm/13.6.777
DO - 10.1093/intimm/13.6.777
M3 - Article
C2 - 11369705
AN - SCOPUS:0034989139
VL - 13
SP - 777
EP - 783
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 6
ER -