| First Author | Ulivieri C | Year | 2000 |
| Journal | Mol Immunol | Volume | 37 |
| Issue | 1-2 | Pages | 85-90 |
| PubMed ID | 10781838 | Mgi Jnum | J:62319 |
| Mgi Id | MGI:1858718 | Doi | 10.1016/s0161-5890(00)00016-x |
| Citation | Ulivieri C, et al. (2000) Restoration of thymic development in an Lck(-/-) thymoma overexpressing ZAP-70. Mol Immunol 37(1-2):85-90 |
| abstractText | Thymic development is strictly controlled by Src and Syk family protein tyrosine kinases. The major players in this process are Lck and ZAP-70, which regulate critical differentiation steps of thymopoiesis. Notwithstanding the critical role of Lck and ZAP-70 in thymocyte development as compared to the related kinases Fyn and Syk, a partial functional redundancy between members of the same family of protein tyrosine kinases has emerged from studies on genetically manipulated mouse models. Furthermore, a close functional interplay between Lck and ZAP-70 in intracellular signaling has been shown to occur in thymocytes. Here we present the characterization of a thymoma from an Lck(-/-) mouse, where the block in thymocyte development is overcome and the transition between the CD4(-)CD8(-) and CD4(+)CD8(+) stages is fully restored. Determination of the expression levels of Fyn, ZAP-70 and Syk in thymocytes form the Lck(-/-) thymoma revealed high levels of ZAP-70 overexpression and recovery of a specific subset of phosphoproteins as compared to Lck(-/-) thymocytes. Hence ZAP-70 overexpression in thymocytes is associated with recovery from the developmental arrest caused by the absence of Lck, suggesting a role for ZAP-70 downstream of Lck in the maturation of CD4(+)CD8(+) thymocytes. |
