Oyaizu N, Than S, McCloskey T W, Pahwa S
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
Biochem Biophys Res Commun. 1995 Aug 24;213(3):994-1001. doi: 10.1006/bbrc.1995.2227.
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.
Fas（CD95）与其配体（Fas-L）的相互作用已被证明在T细胞受体（TCR）/CD3激活诱导的细胞凋亡中起关键作用。尽管有几条证据表明蛋白酪氨酸激酶（PTK）活性参与了这一过程，但src家族PTK p561ck（lck）的作用尚不清楚。我们在此报告，与野生型Jurkat相反，lck缺陷型突变体JCaM对抗CD3诱导的凋亡具有抗性，并且在抗CD3处理后未能表达Fas-L mRNA。然而，发现Jurkat和JCaM都组成性表达Fas，并且对抗Fas介导的凋亡同样敏感。如果用佛波酯（PMA）加离子霉素刺激，JCaM表达Fas-L mRNA并发生凋亡。这些发现表明，p56lck是TCR/CD3介导的Fas-L诱导所必需的，但不是Fas受体介导的死亡信号转导所必需的。
