Differential expression of two lck transcripts directed from the distinct promoters in HTLV-I+ and HTLV-I- T-cells

The lck gene encodes a lymphocyte-specific tyrosine protein kinase, p56lck, the expression of which is almost exclusive in T-cells. The expression of lck in human T-cell leukemia virus type I (HTLV-I)-transformed T-cell lines is closely associated with interleukin-2 (IL-2) dependence for their growth. That is, IL-2-dependent HTLV-I-transformed cell lines contain the lck message abundantly as HTLV-I-negative T-cell lines, whereas IL-2-independent HTLV-I-transformed cell lines express either no or little lck mRNA, although they are derived from T-cells. The lck gene contains 2 distinct promoters which direct 2 types of lck transcript with different 5' untranslated regions. In this study, we show that HTLV-I-transformed IL-2-dependent T-cell lines contain the upstream promoter-initiated lck transcript exclusively, in contrast to HTLV-I-negative transformed T-cell lines which express the down-stream promoter- as well as the upstream promoter-initiated lck transcript. In addition, lck mRNA disappears transiently in IL-2-dependent HTLV-I-transformed T-cell lines after stimulation for T-cell activation, which is also observed in peripheral blood T lymphocytes. These results indicate that the disappearance of lck mRNA in HTLV-I-transformed, IL-2-independent cell lines is caused by a mechanism which down-regulates the upstream promoter-initiated lck transcript and this IL-2-independent state may represent a further "activated" condition of the IL-2-dependent state by the stimulation which mediates T-cell activation.