Artículos de revistas
Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin
Fecha
2003-06-01Registro en:
Molinero, Luciana Lorena; Fuertes, Mercedes Beatriz; Fainboim, Leonardo; Rabinovich, Gabriel Adrián; Zwirner, Norberto Walter; Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 73; 6; 1-6-2003; 815-822
0741-5400
CONICET Digital
CONICET
Autor
Molinero, Luciana Lorena
Fuertes, Mercedes Beatriz
Fainboim, Leonardo
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
Resumen
Major histocompatibility complex class I-related chain (MICA) is a cell stress-regulated molecule recognized by cytotoxic cells expressing the NKG2D molecule. MICA can be induced on T cells after CD3 or CD28 engagement. Here, we investigated the intracellular pathways leading to activation-induced expression of MICA. The Src kinase inhibitor PP1 inhibited up-regulated expression of MICA on anti-CD3-stimulated T cells. Downstream signaling routes involved mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK), p38 MAPK, and calcineurin, as MICA expression was prevented by U0126, SB202190, cyclosporin A, and FK506. Also, Lck and Fyn as well as MEK1/ERK and p38 MAPK were found to regulate MICA expression in anti-CD28/phorbol 12-myristate 13-acetate-stimulated T cells. Expression of MICA on activated T cells involved interleukin-2-dependent signaling routes triggered by Janus tyrosine kinases/signal transducer and activators of transcription and p70S6 kinase, as it could be inhibited by AG490 and rapamycin. This is the first demonstration of the intracellular pathways involved in activation-induced expression of MICA, which may reveal potential targets for immune intervention to modulate MICA expression in pathological disorders.