Protein tyrosine kinase p56 super(l) super(c) super(k)-deficiency confers hypersusceptibility to rho -fluorophenylalanine (pFPhe)-induced apoptosis by augmenting mitochondrial apoptotic pathway in human Jurkat T cells

• Published in: Biochemical and biophysical research communications Vol. 377; no. 1; pp. 280 - 285
• Main Authors: Park, H S, Jun, D Y, Han, C R, Kim, Y H
• Format: Journal Article
• Language: English
• Published: 05.12.2008
• ISSN: 0006-291X
• DOI: 10.1016/j.bbrc.2008.09.126

Phenylalanine analog, rho -fluorophenylalanine (pFPhe)-mediated cytotoxicity and several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9, -3, and -8, Bid cleavage, degradation of PARP and PLC gamma -1, and DNA fragmentation were more significant in p56 super(l) super(c) super(k)-deficient Jurkat T cells (JCaM1.6) than in wild-type Jurkat T cells (E6.1). The susceptibility of JCaM1.6 toward apoptogenic activity of pFPhe decreased after acquisition of p56 super(l) super(c) super(k) by transfection. The p56 super(l) super(c) super(k) kinase activity increased 1.6-fold at 15-30min after pFPhe treatment. The pan-caspase inhibitor (z-VAD-fmk) completely blocked the pFPhe-mediated apoptotic changes except caspase-9 activation. The caspase-8 inhibitor (z-IETD-fmk), which failed to influence pFPhe-induced caspase-9 activation, completely blocked caspase-8 activation and PLC gamma -1 degradation with a marked reduction in caspase-3 activation and PARP degradation, indicating pFPhe-induced caspase-8 activation as a downstream event of mitochondria-dependent activation of caspase-9. These results indicate that the deficiency of p56 super(l) super(c) super(k) augments pFPhe-induced mitochondrial cytochrome c release and resultant apoptotic cell death in Jurkat T cells.