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Science 293 (5538): 2263-2265

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

Coupling of the TCR to Integrin Activation by SLAP-130/Fyb

Erik J. Peterson,12 Melody L. Woods,5 Sally A. Dmowski,1 Geo Derimanov,12 Martha S. Jordan,1 Jennifer N. Wu,1 Peggy S. Myung,1 Qing-Hua Liu,4 Jonathan T. Pribila,5 Bruce D. Freedman,4 Yoji Shimizu,5 Gary A. Koretzky13*

SLAP-130/Fyb (SLP-76-associated phosphoprotein or Fyn-binding protein; also known as Fyb/Slap) is a hematopoietic-specific adapter, which associates with and modulates function of SH2-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76). T cells from mice lacking SLAP-130/Fyb show markedly impaired proliferation following CD3 engagement. In addition, the T cell receptor (TCR) in SLAP-130/Fyb mutant cells fails to enhance integrin-dependent adhesion. Although TCR-induced actin polymerization is normal, TCR-stimulated clustering of the integrin LFA-1 is defective in SLAP-130/Fyb-deficient cells. These data indicate that SLAP-130/Fyb is important for coupling TCR-mediated actin cytoskeletal rearrangement with activation of integrin function, and for T cells to respond fully to activating signals.

1 The Abramson Family Cancer Research Institute, Departments of
2 Medicine and
3 Pathology and Laboratory Medicine, School of Medicine, and the
4 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
5 Department of Pathology and Laboratory Medicine, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
*   To whom correspondence should be addressed. E-mail: koretzky{at}mail.med.upenn.edu

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