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

Abstract

Tyrosine protein kinases are important both in the normal regulation of cellular proliferation and in the oncogenic transformation of cells by several tumour viruses. The LSTRA Moloney murine leukaemia virus (M-MuLV)-induced thymoma cell line contains approximately 20-fold more phosphotyrosine in protein than do typical haematopoietic cell lines; 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 cells. The elevated levels of p56tck could 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. p56tck is encoded in LSTRA cells by a hybrid messenger RNA; approximately 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.