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Publication : Activated p56lck directs maturation of both CD4 and CD8 single-positive thymocytes.

First Author  Sohn SJ Year  2001
Journal  J Immunol Volume  166
Issue  4 Pages  2209-17
PubMed ID  11160274 Mgi Jnum  J:126139
Mgi Id  MGI:3760589 Doi  10.4049/jimmunol.166.4.2209
Citation  Sohn SJ, et al. (2001) Activated p56lck directs maturation of both CD4 and CD8 single-positive thymocytes. J Immunol 166(4):2209-17
abstractText  p56(lck) is a protein tyrosine kinase expressed throughout T cell development. It associates noncovalently with the cytoplasmic domains of the CD4 and CD8 coreceptor molecules and has been implicated in TCR signaling in mature T cells. Its role in early thymocyte differentiation has been demonstrated in vivo, both by targeted gene disruption and by transgene expression. Previously, we showed that expression of a dominant-negative form of p56(lck) in double-positive thymocytes inhibits positive selection. We now demonstrate that expression of constitutively activated p56(lck) (p56(lck)F505) accelerates the transition from the double-positive to the single-positive stage. Importantly, p56(lck)F505 drives survival and lineage commitment of thymocytes in the absence of TCR engagement by appropriate MHC molecules. These results indicate that activation of p56(lck) constitutes an early step in conveying maturational signals after TCR ligation by a positively selecting ligand. Our study provides direct in vivo evidence for the role of p56(lck) in regulating TCR signaling.
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