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The tyrosine kinase...
The tyrosine kinase Lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation
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- Belka, C. (author)
- Department of Radiation Oncology, University of Tuebingen (Germany), Hoppe Seyler Str. 3, 72076 Tuebingen, Germany
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- Marini, P. (author)
- Department of Radiation Oncology, University of Tuebingen (Germany), Hoppe Seyler Str. 3, 72076 Tuebingen, Germany
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- Lepple-Wienhues, A. (author)
- Department of Physiology, University of Tuebingen (Germany), Gmelinstrasse 5, 72076 Tuebingen, Germany
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- Budach, W. (author)
- Department of Radiation Oncology, University of Tuebingen (Germany), Hoppe Seyler Str. 3, 72076 Tuebingen, Germany
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- Jekle, A. (author)
- Department of Physiology, University of Tuebingen (Germany), Gmelinstrasse 5, 72076 Tuebingen, Germany
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- Los, Marek Jan (author)
- Department of Internal Medicine I, University of Tuebingen (Germany), Otfried Müller Str. 10, 72076 Tuebingen, Germany
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- Lang, F. (author)
- Department of Physiology, University of Tuebingen (Germany), Gmelinstrasse 5, 72076 Tuebingen, Germany
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- Schulze-Osthoff, K. (author)
- Department of Internal Medicine I, University of Tuebingen (Germany), Otfried Müller Str. 10, 72076 Tuebingen, Germany
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- Gulbins, E. (author)
- Department of Physiology, University of Tuebingen (Germany), Gmelinstrasse 5, 72076 Tuebingen, Germany
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- Bamberg, M. (author)
- Department of Radiation Oncology, University of Tuebingen (Germany), Hoppe Seyler Str. 3, 72076 Tuebingen, Germany
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Department of Radiation Oncology, University of Tuebingen (Germany), Hoppe Seyler Str 3, 72076 Tuebingen, Germany Department of Physiology, University of Tuebingen (Germany), Gmelinstrasse 5, 72076 Tuebingen, Germany (creator_code:org_t)
- 1999-09-13
- 1999
- English.
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In: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 18:35, s. 4983-4992
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Abstract
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- Induction of apoptosis is a hallmark of cytostatic drug and radiation-induced cell death in human lymphocytes and lymphoma cells. However, the mechanisms leading to apoptosis are not well understood. We provide evidence that ionizing radiation induces a rapid activation of caspase-8 (FLICE) followed by apoptosis independently of CD95 ligand/receptor interaction. The radiation induced cleavage pattern of procaspase-8 into mature caspase-8 resembled that following CD95 crosslinking and resulted in cleavage of the proapoptotic substrate BID. Overexpression of dominant-negative caspase-8 interfered with radiation-induced apoptosis, Caspase-8 activation by ionizing radiation was not observed in cells genetically defective for the Src-like tyrosine kinase Lck, Cells lacking Lck also displayed a marked resistance towards apoptosis induction upon ionizing radiation. After retransfection of Lck, caspase-8 activation and the capability to undergo apoptosis in response to ionizing radiation was restored. We conclude that radiation activates caspase-8 via an Lck-controlled pathway independently of CD95 ligand expression, This is a novel signaling event required for radiation induced apoptosis in T lymphoma cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Apoptosis
- b-cells
- caspase-8/FLICE
- cytochrome-c
- death
- drug-induced apoptosis
- fas-induced apoptosis
- Lck
- leukemia-cells
- ligand expression
- lymphoma
- phosphorylation
- sh2 domain
- t-cells
- tyrosine kinase
Publication and Content Type
- ref (subject category)
- art (subject category)
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Oncogene
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To the university's database
- By the author/editor
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Belka, C.
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Marini, P.
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Lepple-Wienhues, ...
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Budach, W.
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Jekle, A.
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Los, Marek Jan
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show more...
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Lang, F.
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Schulze-Osthoff, ...
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Gulbins, E.
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Bamberg, M.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Oncogene
- By the university
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Linköping University