Restoration of thymic development in an Lck super(-/-) thymoma overexpressing ZAP-70

• Published in: Molecular immunology Vol. 37; no. 1-2; pp. 85 - 90
• Main Authors: Ulivieri, C, Majolini, M B, Baldari, C T
• Format: Journal Article
• Language: English
• Published: 01.02.2000
• Subjects: Lck protein; thymoma; thymopoiesis; ZAP-70 protein
• ISSN: 0161-5890
• DOI: 10.1016/S0161-5890(00)00016-X

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 super(-/-) mouse, where the block in thymocyte development is overcome and the transition between the CD4 super(-)CD8 super(-) and CD4 super(+)CD8 super(+) stages is fully restored. Determination of the expression levels of Fyn, ZAP-70 and Syk in thymocytes form the Lck super(-/-) thymoma revealed high levels of ZAP-70 overexpression and recovery of a specific subset of phosphoproteins as compared to Lck super(-/-) 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 super(+)CD8 super(+) thymocytes.