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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}

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J. Cell Sci. 115, 3039-3048
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Sci. STKE 2002, re3
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Differential Requirement for LAT and SLP-76 in GPVI versus T Cell Receptor Signaling.
B. A. Judd, P. S. Myung, A. Obergfell, E. E. Myers, A. M. Cheng, S. P. Watson, W. S. Pear, D. Allman, S. J. Shattil, and G. A. Koretzky (2002)
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   Abstract »    Full Text »    PDF »

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