Suppression of thymic development by the dominant-negative form of Gads.
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.
Kikuchi
K
K
Department of Microbiology and Immunology, and The Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Kawasaki
Y
Y
Ishii
N
N
Sasaki
Y
Y
Asao
H
H
Takeshita
T
T
Miyoshi
I
I
Kasai
N
N
Sugamura
K
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005799:Genes, Dominant / Q000276:immunology; D006131:Growth Inhibitors / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000254:growth & development*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C409587:GRAP2 protein, human; D006131:Growth Inhibitors; C498726:Mona protein, mouse; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins