| First Author | Baker M | Year | 2000 |
| Journal | EMBO J | Volume | 19 |
| Issue | 17 | Pages | 4644-54 |
| PubMed ID | 10970857 | Mgi Jnum | J:64671 |
| Mgi Id | MGI:1889764 | Doi | 10.1093/emboj/19.17.4644 |
| Citation | Baker M, et al. (2000) Development of T-leukaemias in CD45 tyrosine phosphatase-deficient mutant lck mice. EMBO J 19(17):4644-54 |
| abstractText | 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. |
