p56lck plays a key role in transducing apoptotic signals in T cells.
The CD4 receptor synergizes with the T-cell antigen receptor (TCR) in helper T-cell activation. However CD4 cross-linking in the absence of simultaneous TCR engagement leaves the cells primed to activation dependent apoptosis. To assess the role of the CD4 associated protein tyrosine kinase p56lck in CD4 priming to apoptosis we have constructed Jurkat T-cell lines stably transfected with a constitutively active form of p56lck. These cells were constitutively primed to undergo apoptosis upon TCR crosslinking with specific antibodies. In addition the Jurkat JCaM1 line, which is defective for p56lck expression, was resistant to TCR induced apoptosis. These data indicate that p56lck is required for T-cell apoptosis and that CD4 priming of T-cells for antigen dependent apoptosis is due to inappropriate or partial activation of the p56lck signal transduction pathway.
Di Somma
M M
MM
Department of Evolutionary Biology, University of Siena, Italy.
Nuti
S
S
Telford
J L
JL
Baldari
C T
CT
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000502:physiology; D014162:Transfection
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D003432:Cross-Linking Reagents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000001:Calcimycin; D004247:DNA; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)