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The CD45 tyrosine phosphatase lowers T-cell antigen receptor signalling thresholds by its positive actions on p56(lck) tyrosine kinase function. We now show that mice expressing active lck(F505) at non-oncogenic levels develop aggressive thymic lymphomas on a CD45(-/-) background. CD45 suppresses the tumorigenic potential of the kinase by dephosphorylation of the Tyr394 autophosphorylation site. In CD45(-/-) thymocytes the kinase is switched to a hyperactive oncogenic state, resulting in increased resistance to apoptosis. Transformation occurs in early CD4(-)CD8(-) thymocytes during the process of TCR-beta chain rearrangement by a recombinase-independent mechanism. Our findings represent the first example in which a tyrosine phosphatase in situ prevents the oncogenic actions of a SRC: family tyrosine kinase.

Original publication




Journal article



Publication Date





4644 - 4654


Animals, Apoptosis, Base Sequence, DNA Nucleotidyltransferases, DNA Primers, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Integrases, Leukemia, T-Cell, Leukocyte Common Antigens, Lymphoma, Non-Hodgkin, Mice, Mice, Mutant Strains, Mutation, Protein-Tyrosine Kinases, Recombinases, Thymus Neoplasms, Tumor Cells, Cultured