Requirement for the SLP-76 adaptor GADS in T cell development.
GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined. GADS- CD4-CD8- thymocytes exhibited a severe block in proliferation but still differentiated into mature T cells. GADS- thymocytes failed to respond to CD3 cross-linking in vivo and were impaired in positive and negative selection. Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS- thymocytes. These observations indicate that GADS is a critical adaptor for CD3 signaling.
Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA.
J
J
Yoder
C
C
Pham
Y M
YM
Iizuka
O
O
Kanagawa
S K
SK
Liu
J
J
McGlade
A M
AM
Cheng
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D048429:Cell Size; D005260:Female; D018390:Gene Targeting; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex; D002352:Carrier Proteins; C491734:Lat protein, mouse; D008565:Membrane Proteins; C498726:Mona protein, mouse; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins