Regulated expression of galectin-1 during T-cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p70S6 kinase

Mol Cell Biochem. 2004 Dec;267(1-2):177-85. doi: 10.1023/b:mcbi.0000049376.50242.7f.


Recent evidence has implicated galectins and their carbohydrate ligands as novel regulators of T-cell homeostasis. Galectin-1 (Gal-1), a member of this family, inhibits clonal expansion, induces apoptosis of antigen-primed T lymphocytes and suppresses the development of T-cell-mediated autoimmune diseases in vivo. Because the beta-galactoside-binding protein is expressed in activated but not resting T cells, it has been hypothesized that Gal-1-induced apoptosis may constitute an autocrine suicide mechanism to eliminate activated T cells contributing to the termination of an effector immune response. We undertook this study to investigate the signals and intracellular pathways leading to Gal-1 expression during T-cell activation. When T cells were stimulated either with anti-CD3 or anti-CD28 monoclonal antibody plus PMA in the presence of accessory cells, a sustained up-regulation of Gal-1 was observed, reaching a plateau between days 3 and 5 following CD3 engagement or costimulation through CD28. Investigation of the signal transduction events involved in this process revealed a role for Lck and Fyn kinases, since the Src kinase inhibitor PP1 inhibited the up-regulated expression of Gal-1 following T-cell activation. Downstream signaling routes involve mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK) and p38 MAPK, as Gal-1 expression was prevented by U0126 and SB202190. In addition, expression of Gal-1 involves interleukin (IL)-2-dependent signaling routes triggered by p70S6 kinase, as it could be inhibited by rapamycin. This is the first demonstration of the intracellular pathways that control activation-induced expression of Gal-1, which may reveal potential targets for immune intervention to modulate expression of this beta-galactoside-binding protein in pathological disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Blotting, Western
  • Butadienes / pharmacology
  • Cell Proliferation
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Inhibitors / pharmacology
  • Galectin 1 / genetics
  • Galectin 1 / metabolism*
  • Gene Expression Regulation / immunology*
  • Humans
  • Imidazoles / pharmacology
  • Interleukin-2 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Lymphocyte Activation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
  • MAP Kinase Kinase 1 / metabolism*
  • Models, Biological
  • Nitriles / pharmacology
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-fyn
  • Pyridines / pharmacology
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction
  • Sirolimus / pharmacology
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / metabolism*
  • src-Family Kinases / metabolism*


  • Antibodies, Monoclonal
  • Butadienes
  • Enzyme Inhibitors
  • Galectin 1
  • Imidazoles
  • Interleukin-2
  • Nitriles
  • Proto-Oncogene Proteins
  • Pyridines
  • U 0126
  • FYN protein, human
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases
  • Ribosomal Protein S6 Kinases, 70-kDa
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • Tetradecanoylphorbol Acetate
  • 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
  • Sirolimus