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Interleukin‐2 activates nuclear phospholipase‐Cβ by mitogen‐activated protein kinase‐dependent phosphorylation in human natural killer cells
Author(s) -
Vitale Marco,
Matteucci Alessandro,
Manzoli Lucia,
Rodella Luigi,
Mariani Adriana R.,
Zauli Giorgio,
Falconi Mirella,
Billi Anna Maria,
Martelli Alberto M.,
Gilmour R. Stewart,
Cocco Lucio
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0008fje
Subject(s) - phosphorylation , protein kinase a , microbiology and biotechnology , mitogen activated protein kinase , chemistry , kinase , map kinase kinase kinase , biology
It is not yet clear whether nuclear phospholipase C (PLC) signaling is implicated in the response of primary cells to cytokines or not and, in particular, whether lymphocytes utilize the nuclear phosphoinositides breakdown as a step in the signal transduction generated by cytokine receptor triggering. Therefore, we have studied the repertoire and functional regulation of nuclear PLC, the key enzyme of phosphoinositides turnover, by interleukin‐2 (IL‐2) in primary human natural killer (NK) cells and its effects on the IL‐2‐driven NK cell proliferation. We found that 1) IL‐2 stimulates nuclear PLC activity within 60 min of treatment; 2) NK cells express only the β family of PLCs in the nucleus, and the isoform of this enzyme regulated by IL‐2 is PLCβ 1 b; 3) IL‐2 induces nuclear translocation of extracellular signal‐related kinase (ERK)‐2, or p42, and to a lesser extent, of ERK‐1, or p44, of mitogen‐activated protein kinase (MAPK), whose specific inhibition prevents the IL‐2‐driven nuclear PLCβ 1 activation; 4) PLCβ 1 b is serine‐phosphorylated after IL‐2, and the phosphorylation is abolished after MAPK inhibition; and 5) inhibition of nuclear PLC activation leads to the inhibition of the IL‐2‐induced proliferation of NK cells. Altogether, our data indicate that nuclear PLC signaling is a downstream target of the ERK/MAPK pathway stimulated by IL‐2 receptor triggering in human primary NK cells, and that the nuclear phosphoinositides turnover is a key step in proliferative response of NK cells to IL‐2.