Activated p56(lck) directs maturation of both CD4 and CD8 single-positive thymocytes

p56(lck) is a protein tyrosine kinase expressed throughout T cell developme nt, It associates noncovalently with the cytoplasmic domains of the CD4 and CD8 coreceptor molecules and has been implicated in TCR signaling in matur e T cells. Its role in early thymocyte differentiation has been demonstrate d in vivo, both by targeted gene disruption and by transgene expression. Pr eviously, we showed that expression of a dominant-negative form of p56(lck) in double-positive thymocytes inhibits positive selection. We now demonstr ate that expression of constitutively activated p56(lck) (p56(lck)F505) acc elerates the transition from the double-positive to the single-positive sta ge, Importantly, p56(lck)F505 drives survival and lineage commitment of thy mocytes in the absence of TCR engagement by appropriate MHC molecules. Thes e results indicate that activation of p56(lck) constitutes an early step in conveying maturational signals after TCR ligation by a positively selectin g ligand. Our study provides direct in vivo evidence for the role of p56(lc k) in regulating TCR signaling.