Requirement of p56lck in T-cell receptor/CD3-mediated apoptosis and Fas-ligand induction in Jurkat cells.
Interactions of Fas (CD95) and its ligand (Fas-L) has been shown to play a pivotal role in T cells receptor (TCR)/CD3 activation-induced cell death via apoptosis. Although several lines of evidence suggest involvement of protein tyrosine kinase (PTK) activity in this process, the role of src family PTK p561ck (lck) is not known. We report here that, contrary to wild type Jurkat, the lck-deficient mutant JCaM is resistant to anti-CD3-induced apoptosis and fails to express Fas-L mRNA upon anti-CD3 treatment. However, both Jurkat and JCaM were found to constitutively express Fas and were equally sensitive to anti-Fas-mediated apoptosis. If stimulated with PMA plus ionomycin, JCaM expressed Fas-L mRNA and underwent apoptosis. These findings indicate that p56lck is required for TCR/CD3-mediated Fas-L induction but not for the transduction of Fas receptor-mediated death signal.
Oyaizu
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Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
Than
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McCloskey
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TW
Pahwa
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S
D000954:Antigens, Surface; D017209:Apoptosis; D001483:Base Sequence; D016227:Benzoquinones; D017252:CD3 Complex / Q000502:physiology*; D053222:Fas Ligand Protein; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D000954:Antigens, Surface; D016227:Benzoquinones; D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D047029:Lactams, Macrocyclic; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011809:Quinones; D019014:fas Receptor; D017828:Rifabutin; D015759:Ionomycin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D013755:Tetradecanoylphorbol Acetate