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
