INVESTIGADORES
RABINOVICH Gabriel Adrian
artículos
Título:
REGULATED EXPRESSION OF GALECTIN-1 DURING T CELL ACTIVATION INVOLVES LCK, FYN KINASES AND SIGNALING THROUGH MEK1/ERK, p38 MAP KINASE AND p70S6 KINASE
Autor/es:
MERCEDES B. FUERTES,; LUCIANA MOLINERO,; MARTA A. TOSCANO,; JUAN M. ILARREGUI,; NATALIA RUBINSTEIN,; LEONARDO FAINBOIM,; NORBERTO W. ZWIRNER*,; GABRIEL A. RABINOVICH*
Revista:
MOLECULAR AND CELLULAR BIOCHEMISTRY
Editorial:
Springer Link
Referencias:
Lugar: The Netherlands; Año: 2004 vol. 267 p. 177 - 185
ISSN:
0300-8177
Resumen:
Recent evidence has implicated galectins and their carbohydrate ligands as novel regulators of T-cell homeostasis. Galectin-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 this b-galactoside-binding protein is expressed in activated but not resting T cells, it has been hypothesized that galectin-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 galectin-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 galectin-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 galectin-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 galectin-1 expression was prevented by U0126 and SB202190. In addition, expression of galectin-1 involves interleukin-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 galectin-1, which may reveal potential targets for immune intervention to modulate expression of this b-galactoside-binding protein in pathological disorders.