Expression of a new tyrosine protein kinase is stimulated by retrovirus promoter insertion

Tyrosine protein kinases are important both in the normal regulation of cellular proliferation and in the oncogenic transformation of cells by several tumour viruses1. The LSTRA Moloney murine leukaemia virus (M-MuLV)-induced thymoma cell line2contains ∼20-fold more phosphotyrosine in protein than do typical haematopoietic cell lines3; this seems to result from the expression of an abnormally high level of a cellular tyrosine protein kinase termed p56tck(refs 3,4). This kinase is normally expressed at low levels in most, but not all, murine T cells3,4. The elevated levels of p56tckcould contribute to the malignant properties of LSTRA cells. Therefore, we have isolated cloned complementary DNAs encoding the whole of p56tck. Sequence analysis shows it to be a novel cellular tyrosine protein kinase which is distinct from all others described to date. p56tckis encoded in LSTRA cells by a hybrid messenger RNA; ∼200 nucleotides at the 5′ end of the mRNA are identical to the 5′ end of the genome of M-MuLV. The three- to ninefold transcriptional activation of the gene therefore results from retroviral promoter insertion.