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Science 291 (5510): 1987-1991

Copyright © 2001 by the American Association for the Advancement of Science

Requirement for the SLP-76 Adaptor GADS in T Cell Development

Jeff Yoder,1 Christine Pham,234 Yoshie-Matsubayashi Iizuka,3 Osami Kanagawa,4 Stanley K. Liu,5 Jane McGlade,5 Alec M. Cheng234*

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.

1 Medical Scientist Training Program;
2 Center for Immunology;
3 Division of Rheumatology, Department of Medicine;
4 Department of Pathology and Immunology; Washington University School of Medicine, St. Louis, MO 63110, USA.
5 Hospital for the Sick Children, University of Toronto, Toronto, Canada.
*   To whom correspondence should be addressed. E-mail:acheng{at}im.wustl.edu

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