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Science 293 (5538): 2260-2263

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

Positive Regulation of T Cell Activation and Integrin Adhesion by the Adapter Fyb/Slap

Emily K. Griffiths,12 Connie Krawczyk,12 Young-Yun Kong,12 Monika Raab,3 Sharon J. Hyduk,4 Denis Bouchard,1 Vera S. Chan,2 Ivona Kozieradzki,12 Antonio J. Oliveira-dos-Santos,12 Andrew Wakeham,1 Pamela S. Ohashi,2 Myron I. Cybulsky,4 Christopher E. Rudd,3 Josef M. Penninger12*

The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb/Slap is also required in vivo for T cell-dependent immune responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion.

1 Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.
2 Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
3 Division of Tumor Immunology, Dana-Farber Cancer Institute, and Departments of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.
4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Canada.
*   To whom correspondence should be addressed. E-mail: jpenning{at}amgen.com


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