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.