Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines

摘要: The lymphokine interleukin-3 (IL-3) promotes the growth and survival of immature hematopoietic cells. Previous studies have shown that IL-3 induces rapid increases in protein-tyrosine kinase (PTK) activity IL- 3--dependent Unlike some other factor receptors (eg, c-fms c-kit), however, known subunits 3 receptor (IL-3R) lack intrinsic activity. Recently, it was reported IL-2R (whose p75 beta-subunit shares sequence homology with a murine IL-3R subunit common human granulocyte-macrophage colony-stimulating [GM-CSF] receptors) can physically associate regulate SRC-family PTK, p56-LCK. Because most IL-3--dependent cells contain p53/56-LYN, but not p56-LCK, we explored effects on activities LYN SRC-like PTKs two leukemic cell lines, AML-193 TALL-101, which are phenotypically myeloid, whose vitro is dependent IL-3. These expressed four eight proto-oncogenes: lyn, fyn, yes, hck. When these factor-dependent lines were deprived to achieve cellular quiescence then restimulated IL-3, (detectable within 1 minute maximal by 10 minutes) observed p53/56-LYN kinase, as assessed assays. In contrast, no alteration present detected after restimulation under same conditions. This effect reflected an increase specific because levels 53-Kd 56-Kd proteins unaltered stimulation, immunoblotting. Furthermore, magnitude inducible concentration correlated IL-3--induced proliferation. upregulation may be mediated 120-Kd GM-CSF receptors, also stimulated marked whereas granulocyte-CSF (G-CSF) did not, despite inducing observations provide first example IL-3-- regulable strongly suggest participates early IL-3--initiated signalling events, at least lines.