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Science ; 293(5538): 2263-5, 2001 Sep 21.
Article in English | MEDLINE | ID: mdl-11567141

ABSTRACT

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.


Subject(s)
Adaptor Proteins, Signal Transducing , Carrier Proteins/metabolism , Lymphocyte Function-Associated Antigen-1/physiology , Phosphoproteins/metabolism , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/physiology , Actins/metabolism , Animals , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , CD3 Complex/immunology , Carrier Proteins/genetics , Cell Adhesion , Cell Membrane/metabolism , Immunologic Capping , Intercellular Adhesion Molecule-1/metabolism , Interleukin-2/biosynthesis , Interleukin-2/pharmacology , Lectins, C-Type , Lymphocyte Activation , Mice , Phosphatidylinositol 3-Kinases/metabolism , Phosphoproteins/genetics , Protein-Tyrosine Kinases/metabolism , Receptors, Interleukin-2/metabolism , Signal Transduction , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
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