Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.1093/emboj/19.17.4644

Type

Journal article

Journal

EMBO J

Publication Date

01/09/2000

Volume

19

Pages

4644 - 4654

Keywords

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