Up-regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases, and signaling through MEK1/ERK, p38 MAP kinase and calcineurin

MOLINERO, LUCIANA LORENA; FUERTES, MERCEDES BEATRIZ; FAINBOIM, LEONARDO; RABINOVICH, GABRIEL ADRIÁN; ZWIRNER, NORBERTO WALTER

JOURNAL OF LEUKOCYTE BIOLOGY

Society for Leukocyte Biology

Lugar: Bethesda; Año: 2003 vol. 73 p. 815 - 822

0741-5400

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. Dowstream signaling routes involved MEK1/ERK, p38 MAPK and calcineurin, since 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/PMA-stimulated T cells. Expression of MICA on activated T cells involved IL-2-dependent signaling routes triggered by Jaks/STATs and p70S6 kinase, since 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.