Activated p56lck directs maturation of both CD4 and CD8 single-positive thymocytes.
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.
Sohn
S J
SJ
Department of Immunology, University of Washington, Seattle, WA 98195, USA. sjsohn@uclink4.berkeley.edu
Forbush
K A
KA
Pan
X C
XC
Perlmutter
R M
RM
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis*; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D016130:Immunophenotyping; D018655:Lymphocyte Count; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)