Coupling of the TCR to integrin activation by Slap-130/Fyb

Science. 2001 Sep 21;293(5538):2263-5. doi: 10.1126/science.1063486.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Carrier Proteins
  • Fyb protein, mouse
  • Interleukin-2
  • Lectins, C-Type
  • Lymphocyte Function-Associated Antigen-1
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Intercellular Adhesion Molecule-1
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases