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

• Published in: Science (American Association for the Advancement of Science) 2001-09, Vol.293 (5538), p.2263-2265
• Main Authors: Peterson, Erik J., Woods, Melody L., Dmowski, Sally A., Derimanov, Geo, Jordan, Martha S., Wu, Jennifer N., Myung, Peggy S., Liu, Qing-Hua, Pribila, Jonathan T., Freedman, Bruce D., Shimizu, Yoji, Koretzky, Gary A.
• Format: Article
• Language: English
• Subjects: Actins; Actins - metabolism; Adaptor Proteins, Signal Transducing; Analysis; Animals; Antigen receptors, T cell; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; Biochemistry; Biological and medical sciences; Calcium; Carrier Proteins - genetics; Carrier Proteins - metabolism; CD3 Complex - immunology; Cell Adhesion; Cell Membrane - metabolism; Cell research; Cells; Cellular biology; Cytokines; Cytological research; Fluorescence; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Fyb protein; Hematopoietic agents; Immunobiology; Immunologic Capping; Integrins; Intercellular Adhesion Molecule-1 - metabolism; Interleukin-2 - biosynthesis; Interleukin-2 - pharmacology; Lectins, C-Type; Lymphocyte Activation; Lymphocyte Function-Associated Antigen-1 - physiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Microscopy; Phosphatidylinositol 3-Kinases - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protein tyrosine kinase; Protein-Tyrosine Kinases - metabolism; Proteins; Receptors; Receptors, Antigen, T-Cell - metabolism; Receptors, Interleukin-2 - metabolism; Signal Transduction; SLAP protein; Stem cells; T cell antigen receptors; T cells; T lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - physiology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1063486

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.