ArticleProceedings of the National Academy of Sciences of the United States of America1994
The c-kit ligand suppresses apoptosis of human natural killer cells through the upregulation of bcl-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 147 citations in OpenAlex.
- RNA helicase DDX3X promotes NK cell survival by supporting MCL1 expression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Sodium butyrate supresses malignant human mast cell proliferation, downregulates expression of KIT and promotes differentiation.Frontiers in allergy · 2023Article
- HCMV Infection in a Mesenchymal Stem Cell Niche: Differential Impact on the Development of NK Cells versus ILC3.Journal of clinical medicine · 2019Article
- Alterations of oncogenes expression in NK cells in patients with cancer.Immunity, inflammation and disease · 2017Article
- The Broad Spectrum of Human Natural Killer Cell Diversity.Immunity · 2017Review
- Practical NK cell phenotyping and variability in healthy adults.Immunologic research · 2015Article
- Transmyocardial Revascularization Enhances Bone Marrow Stem Cell Engraftment in Infarcted Hearts Through SCF-C-kit and SDF-1-CXCR4 Signaling Axes.Stem cell reviews and reports · 2015Article
- Location and cellular stages of natural killer cell development.Trends in immunology · 2013Review
- Genetic interaction between Kit and Scl.Blood · 2013Article
- Phase I clinical trial combining imatinib mesylate and IL-2 in refractory cancer patients: IL-2 interferes with the pharmacokinetics of imatinib mesylate.Oncoimmunology · 2013Article
- Article
- Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15.Experimental hematology · 2008Article
- TGFbeta promotes conversion of CD16+ peripheral blood NK cells into CD16- NK cells with similarities to decidual NK cells.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Targeting the c-kit receptor in the treatment of acute myelogenous leukemia.Current hematologic malignancy reports · 2006Review
- Interactions between natural killer cells, cortisol and prolactin in malaria during pregnancy.Clinical medicine & research · 2006Review
- A high-efficiency system of natural killer cell cloning.Journal of immunological methods · 2005Article
- Kit signaling and negative regulation of daunorubicin-induced apoptosis: role of phospholipase Cgamma.Oncogene · 2001Article
- Essential requirement for c-kit and common gamma chain in thymocyte development cannot be overruled by enforced expression of Bcl-2.The Journal of experimental medicine · 2001Article
- Hematopoietic stem cells need two signals to prevent apoptosis; BCL-2 can provide one of these, Kitl/c-Kit signaling the other.The Journal of experimental medicine · 2000Article
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The bcl-2 protein plays a central role in the regulation of programmed cell death in a variety of tissues and is pivotal to the survival of lymphocytes in vivo. The growth factors responsible for survival of normal lymphocytes are unknown but are likely to maintain viability in part through the regulation of bcl-2 expression. A subset of human natural killer (NK) cells (CD3-CD56bright) are unique among lymphocytes in their constitutive expression of c-kit, a tyrosine kinase cell surface receptor that binds c-kit ligand (KL). Alone, KL does not promote proliferation or further differentiation of CD56bright NK cells. We now report that, in the absence of serum or additional growth factors, KL prevents apoptosis of cultured CD56bright NK cells, as assessed by DNA fragmentation studies, and maintains viability, as measured by biologic responses (i.e., proliferation and cytotoxicity) to the subsequent addition of other cytokines. Furthermore, we demonstrate that KL induces CD56bright NK cells to express the bcl-2 protein. In the presence of anti-c-kit antibody, the tyrosine kinase inhibitor genistein, or bcl-2 antisense oligonucleotide, the protective effect of KL on the survival of CD56bright NK cells is dramatically reduced. These data demonstrate that the binding of KL to its tyrosine kinase receptor results in the upregulation of bcl-2, thereby preventing apoptosis in this subset of normal human lymphocytes. As soluble KL is plentiful in normal human serum, this survival mechanism may be operative for CD56bright NK cells in vivo.
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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.