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Up‐regulated expression of MICA on activated T lymphocytes involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase, and calcineurin
Author(s) -
Molinero Luciana L.,
Fuertes Mercedes B.,
Fainboim Leonardo,
Rabinovich Gabriel A.,
Zwirner Norberto W.
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0602329
Subject(s) - microbiology and biotechnology , biology , mapk/erk pathway , fyn , kinase , signal transduction , janus kinase , tyrosine kinase , mitogen activated protein kinase , protein kinase a
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 p70 S 6 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.