Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap

Science. 2001 Sep 21;293(5538):2260-3. doi: 10.1126/science.1063397.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • B-Lymphocytes / immunology
  • CD3 Complex / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Chimera
  • Gene Targeting
  • Humans
  • Immunization
  • Immunoglobulin G / biosynthesis
  • Integrins / metabolism*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / pharmacology
  • Lectins, C-Type
  • Lymphocyte Activation*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Recombinant Proteins / 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
  • Cell Adhesion Molecules
  • FYB1 protein, human
  • Fyb protein, mouse
  • ICAM2 protein, human
  • Immunoglobulin G
  • Integrins
  • Interleukin-2
  • Lectins, C-Type
  • Lymphocyte Function-Associated Antigen-1
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma