Suppression of thymic development by the dominant-negative form of Gads
Suppression of thymic development by the dominant-negative form of Gads
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DOI：
10.1093/intimm/13.6.777
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发表时间：
2001-06-01
影响因子：
4.4
通讯作者：
Sugamura, K
中科院分区：
文献类型：
--
作者：
Kikuchi, K;Kawasaki, Y;Sugamura, K
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.
