Development of T-leukaemias in CD45 tyrosine phosphatase-deficient mutant lck mice

AUTOR(ES)

Baker, Matthew

FONTE

Oxford University Press

RESUMO

The CD45 tyrosine phosphatase lowers T-cell antigen receptor signalling thresholds by its positive actions on p56lck tyrosine kinase function. We now show that mice expressing active lckF505 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-β 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.

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