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

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Abstract
The lck gene encodes a lymphocyte‐specific tyrosine protein ktnase,p56lck, the expression of which is almost exclusive In T‐cells. The expression of lck in human T‐cell leukemia virus type I (HTLV‐1)‐transformed T‐cell lines is closely associated with interleukin‐2 (IL‐2) dependence for their growth. That is, IL‐2‐dependent HTLV‐1‐transformed cell lines contain the lck message abundantly as HTLV‐1‐negative T‐cell lines, whereas IL‐2‐Independent HTLV‐1‐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 S′ untranslated regions. In this study, we show that HTLV‐1‐transformed IL‐2‐dependent T‐cell lines contain the upstream promoter‐initiated lck transcript exclusively, in contrast to HTLV‐1‐negative transformed T‐cell lines which express the downstream promoter‐as well as the upstream promoter‐initiated lck transcript. In addition, lck mRNA disappears transiently in IL‐2‐dependent HTLV‐1‐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‐1‐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.