ArticleThe Journal of biological chemistry2009
The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Current utilization trend of immortalized mast cell lines in allergy research: a systematic review.Immunologic research · 2025Pooled it
- SOCS2 inhibits the tumorigenesis of GISTs and increases the sensitivity of GISTs to imatinib by suppression of KIT activation.Scientific reports · 2025Article
- RAF1 facilitates KIT signaling and serves as a potential treatment target for gastrointestinal stromal tumor.Oncogene · 2024Article
- SPRY4 inhibits and sensitizes the primary KIT mutants in gastrointestinal stromal tumors (GISTs) to imatinib.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Penttinen syndrome-associated PDGFRB Val665Ala variant causes aberrant constitutive STAT1 signalling.Journal of cellular and molecular medicine · 2022Article
- A novel anti-c-Kit antibody-drug conjugate to treat wild-type and activating-mutant c-Kit-positive tumors.Molecular oncology · 2022Article
- Protein tyrosine phosphatase receptor type E (PTPRE) regulates the activation of wild-type KIT and KIT mutants differently.Biochemistry and biophysics reports · 2021Article
- Evolution of KIPPIS as a versatile platform for evaluating intracellularly functional peptide aptamers.Scientific reports · 2021Article
- Computational studies of anaplastic lymphoma kinase mutations reveal common mechanisms of oncogenic activation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Persistent Human KIT Receptor Signaling Disposes Murine Placenta to Premature Differentiation Resulting in Severely Disrupted Placental Structure and Functionality.International journal of molecular sciences · 2020Article
- Review
- Computational algorithms for in silico profiling of activating mutations in cancer.Cellular and molecular life sciences : CMLS · 2019Review
- Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration.Frontiers in immunology · 2019Article
- Gene networks in basal cell carcinoma of the eyelid, analyzed using gene expression profiling.Oncology letters · 2018Article
- Preclinical human models and emerging therapeutics for advanced systemic mastocytosis.Haematologica · 2018Review
- XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation.Oncogenesis · 2018Article
- Evolution of oncogenic signatures of mutation hotspots in tyrosine kinases supports the atavistic hypothesis of cancer.Scientific reports · 2018Article
- Internal tandem duplication mutations in the tyrosine kinase domain of FLT3 display a higher oncogenic potential than the activation loop D835Y mutation.Annals of hematology · 2018Article
- Oncogenic KIT mutations in different exons lead to specific changes in melanocyte phospho-proteome.Journal of proteomics · 2016Article
- Germline mutations of KIT in gastrointestinal stromal tumor (GIST) and mastocytosis.Cell & bioscience · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor tyrosine kinase c-Kit plays a critical role in hematopoiesis, and gain-of-function mutations of the receptor are frequently seen in several malignancies, including acute myeloid leukemia, gastrointestinal stromal tumors, and testicular carcinoma. The most common mutation of c-Kit in these disorders is a substitution of the aspartic acid residue in position 816 to a valine (D816V), leading to constitutive activation of the receptor. In this study, we aimed to investigate the role of Src family kinases in c-Kit/D816V signaling. Src family kinases are necessary for the phosphorylation of wild-type c-Kit as well as of activation of downstream signaling pathways including receptor ubiquitination and the Ras/Mek/Erk pathway. Our data demonstrate that, unlike wild-type c-Kit, the phosphorylation of c-Kit/D816V is not dependent on Src family kinases. In addition, we found that neither receptor ubiquitination nor Erk activation by c-Kit/D816V required activation of Src family kinases. In vitro kinase assay using synthetic peptides revealed that c-Kit/D816V had an altered substrate specificity resembling Src and Abl tyrosine kinases. We further present evidence that, in contrast to wild-type c-Kit, Src family kinases are dispensable for c-Kit/D816V cell survival, proliferation, and colony formation. Taken together, we demonstrate that the signal transduction pathways mediated by c-Kit/D816V are markedly different from those activated by wild-type c-Kit and that altered substrate specificity of c-Kit circumvents a need for Src family kinases in signaling of growth and survival, thereby contributing to the transforming potential of c-Kit/D816V.
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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.