Abstract
To evaluate the role of the human T-cell-specific tyrosine kinase lck (YT16), we measured the levels of lck expression in thymocytes, peripheral T-cells, and leukemia T-cell lines which are arrested at different stages of thymic differentiation. The results indicate that higher levels of the lck message can be found in total thymocytes and T-cells arrested at Stage III (thymocytes that have rearranged their α, β, and γ chain T-cell receptor genes). A 20-fold lower level of these transcripts, however, can be found in cells derived from Stage I cells (thymocytes with germline α, β, and γ genes), 4 times less messages in Stage II cells (thymocytes with rearranged γ and β chain genes, but with germline α chain genes), and a 4-fold lower amount of RNA in Stage IV cells (mature lymphocytes). Culture of these cells with a variety of inducing reagents indicated that leukemia cell lines of only Stages I and II can be induced to increase their levels of YT16 expression by the addition of tetradecanoyl phorbol-13-acetate. These results suggest that there may be a developmental regulation of these tyrosine kinase messages during T-cell ontogeny. The high level of these transcripts in more mature T-cell leukemia lines suggests that they may primarily play a role in the proliferative controls of these cells.
This work is supported by the Medical Research Council of Canada, the National Cancer Institute of Canada, and the National Sciences and Engineering Research Council of Canada.