ArticleOncogene2006
The tyrosine kinase Lck is a positive regulator of the mitochondrial apoptosis pathway by controlling Bak expression.
Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 44 citations in OpenAlex.
- New insights into the Lck-NF-κB signaling pathway.Frontiers in cell and developmental biology · 2023Review
- GCancers · 2020Article
- Compounds from Natural Sources as Protein Kinase Inhibitors.Biomolecules · 2020Review
- Three new compounds with nitric oxide inhibitory activity fromBMC chemistry · 2019Article
- Cis-trimethoxy resveratrol induces intrinsic apoptosis via prometaphase arrest and prolonged CDK1 activation pathway in human Jurkat T cells.Oncotarget · 2018Article
- Article
- Lck is a relevant target in chronic lymphocytic leukaemia cells whose expression variance is unrelated to disease outcome.Scientific reports · 2017Article
- Article
- Lymphocyte cell kinase activation mediates neuroprotection during ischemic preconditioning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Molecular characterization, tissue expression, polymorphism and association of porcine LCK gene.Molecular biology reports · 2012Article
- Antiproliferative and proapoptotic activity of GUT-70 mediated through potent inhibition of Hsp90 in mantle cell lymphoma.British journal of cancer · 2011Article
- Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30+ T-cell lymphoproliferations.Haematologica · 2010Article
- Breast cancer patients' clinical outcome measures are associated with Src kinase family member expression.British journal of cancer · 2010Article
- Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma.Blood · 2010Article
- Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance.The Journal of clinical investigation · 2010Article
- LCK, survivin and PI-3K in the molecular biomarker profiling of oral lichen planus and oral squamous cell carcinoma.Bioinformation · 2009Article
- Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.Nucleic acids research · 2009Article
- Article
- Review
Corrections and comments
- Commented on by
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinases of the Src family have been implicated in key biological processes. Here, we provide evidence that p56(Lck), a lymphoid-specific Src kinase, is involved in the activation of the mitochondrial apoptosis pathway. Lck-deficient T cells were completely resistant to anticancer drugs. In contrast, apoptosis sensitivity to death receptors was not altered, indicating a specific interference of Lck with the mitochondrial pathway. Re-expression of Lck restored sensitivity to drug-induced apoptosis and triggered mitochondrial cytochrome c release and caspase activation. Further analysis identified that the sensitization by Lck was independent of classical mediators of T-cell signaling, but essentially involved the Bcl-2 protein Bak. Expression of Bak was completely absent in Lck-deficient cells, while re-expression of Lck transcriptionally triggered Bak expression and conferred sensitivity to apoptosis, associated with a proapoptotic conformational change of Bak. Furthermore, in vitro the truncated fragment of Bid specifically activated Bak and cytochrome c release only from mitochondria of Lck-expressing cells. These results do not only demonstrate a sentinel role of Lck in drug resistance but also delineate a hitherto unknown pathway of Src kinases in regulation of Bcl-2 proteins.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.