Phosphorylation of src family lck tyrosine kinase following interleukin-12 activation of human natural killer cells

Claudio Pignata, Kanteti V.S. Prasad, Michael Hallek, Brian Druker, Christopher E. Rudd, Michael J. Robertson, Jerome Ritz

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Interleukin-12 (IL-12) is a heterodimeric cytokine that augments the cytolytic activity of human NK cells and T cells but has little mitogenic activity on resting lymphocytes. The intracellular signaling pathways involved in NK cell activation by IL-12 have not been fully characterized. In the present studies we found that IL-12 induces tyrosine phosphorylation of a 56-kDa protein, identified in Western blot experiments as p56lck, in resting NK cells. IL-12 was active in the range of 0.1 to 1000 U/ml, with maximal activity between 10 and 100 U/ml (30 and 300 pM). The maximal effect was noted 5 rain after stimulation and was almost completely inhibited by genistein. IL-12 induced similar effects in resting and IL-2-activated NK cells. Following IL-12 stimulation of resting NK cells, immunoprecipitated lck kinase exhibited increased in vitro autophosphorylation activity 5 and 10 rain after activation. Several additional substrates were phosphorylated in vitro following IL-12 stimulation, including proteins of 70 and 110 kDa. These studies indicate that lck tyrosine kinase is involved in the IL-12 signaling pathway in human NK cells. As the primary functional effect of IL-12 on resting NK cells is the enhancement of cytolytic activity and secretory function rather than cell proliferation, these findings suggest that lck tyrosine kinase is involved in these signaling pathways in human NK cells.

Original languageEnglish (US)
Pages (from-to)211-216
Number of pages6
JournalCellular Immunology
Volume165
Issue number2
DOIs
StatePublished - Oct 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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