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The tyrosine kinase Lck is involved in regulation of mitochondrial apoptosis pathways.
- Source :
-
Oncogene [Oncogene] 2003 Jan 16; Vol. 22 (2), pp. 176-85. - Publication Year :
- 2003
-
Abstract
- The induction of apoptosis requires the activation of a highly coordinated signaling network ultimately leading to the activation of caspases. In previous experiments we and others have shown that the tyrosine kinase Lck is required for adequate apoptosis induction in response to ionizing radiation, ceramide incubation and overexpression of the HIV-TAT protein. However, the position of Lck within given apoptotic signaling cascades remains unclear. We therefore aimed to define the role of Lck during radiation-induced apoptosis. Apoptosis induction in response to ionizing radiation, CD95 or TRAIL receptor stimulation was determined in Jurkat T-cells, the Lck-deficient Jurkat clone JCaM1.6- and Lck-retransfected JCaM1.6/Lck. No apoptosis, release of cytochrome c, breakdown of the mitochondrial potential were detectable during the first 48 h after irradiation of JCaM1.6 cells. In parallel, no activation of caspase-9, -8 and -3 was detectable. Since mitochondrial apoptosis pathways act within a feedback mechanism during death-receptor-mediated apoptosis, the influence of the Lck defect on CD95/Fas/Apo-1-L or TRAIL-induced apoptosis was also tested. Both stimuli induced apoptosis in Lck-deficient cells. However, the kinetics of apoptosis induction determined by caspase-8, -9 and -3 activation as well as deltapsi(m) breakdown was slowed. We conclude that the Lck deficiency influences early steps during radiation-induced mitochondrial alterations.
- Subjects :
- Apoptosis drug effects
Apoptosis radiation effects
Apoptosis Regulatory Proteins
CD3 Complex drug effects
CD3 Complex metabolism
Caspase 3
Caspase 8
Caspase 9
Caspases metabolism
Cytochrome c Group metabolism
Cytochrome c Group radiation effects
Humans
Jurkat Cells drug effects
Jurkat Cells radiation effects
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) genetics
Membrane Glycoproteins metabolism
Membrane Potentials radiation effects
Mitochondria radiation effects
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases metabolism
Phytohemagglutinins pharmacology
Proto-Oncogene Proteins c-bcl-2 metabolism
Proto-Oncogene Proteins c-bcl-2 radiation effects
Radiation, Ionizing
Signal Transduction
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha metabolism
fas Receptor metabolism
Apoptosis physiology
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) metabolism
Mitochondria metabolism
Plant Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 22
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 12527887
- Full Text :
- https://doi.org/10.1038/sj.onc.1206103