Suppression of thymic development by the dominant-negative form of Gads

Kazu Kikuchi, Yoshitada Kawasaki, Naoto Ishii, Yoshiteru Sasaki, Hironobu Asao, Toshikazu Takeshita, Ichiro Miyoshi, Noriyuki Kasai, Kazuo Sugamura

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)777-783
Number of pages7
JournalInternational immunology
Volume13
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • Grb2 family
  • LAT
  • Pre-TCR signaling
  • SLP-76
  • TCR signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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