ArticleOncogene2014
The PI3-kinase isoform p110δ is essential for cell transformation induced by the D816V mutant of c-Kit in a lipid-kinase-independent manner.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- The Mechanisms of Imatinib Resistance in Gastrointestinal Stromal Tumours: Theoretical Basis and Therapeutic Aspect.Journal of cellular and molecular medicine · 2025Review
- 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
- Protein tyrosine phosphatase receptor type E (PTPRE) regulates the activation of wild-type KIT and KIT mutants differently.Biochemistry and biophysics reports · 2021Article
- Loss of PI3 kinase association improves the sensitivity of secondary mutation of KIT to Imatinib.Cell & bioscience · 2020Article
- Case Study: Mechanism for Increased Follicular Helper T Cell Development in Activated PI3K Delta Syndrome.Frontiers in immunology · 2019Article
- Bruton's tyrosine kinase potentiates ALK signaling and serves as a potential therapeutic target of neuroblastoma.Oncogene · 2018Article
- XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation.Oncogenesis · 2018Article
- Aberrant activation of the PI3K/mTOR pathway promotes resistance to sorafenib in AML.Oncogene · 2016Article
- FYN expression potentiates FLT3-ITD induced STAT5 signaling in acute myeloid leukemia.Oncotarget · 2016Article
- Germline mutations of KIT in gastrointestinal stromal tumor (GIST) and mastocytosis.Cell & bioscience · 2016Review
- PI3 kinase is indispensable for oncogenic transformation by the V560D mutant of c-Kit in a kinase-independent manner.Cellular and molecular life sciences : CMLS · 2015Article
- SOCS6 is a selective suppressor of receptor tyrosine kinase signaling.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PI3-kinase has a crucial role in transformation mediated by the oncogenic c-Kit mutant D816V. In this study, we demonstrate that the c-Kit/D816V-mediated cell survival is dependent on an intact direct binding of PI3-kinase to c-Kit. However, mutation of this binding site had little effect on the PI3-kinase activity in the cells, suggesting that c-Kit/D816V-mediated cell survival is dependent on PI3-kinase but not its kinase activity. Furthermore, inhibition of the lipid kinase activity of PI3-kinase led only to a slight inhibition of cell survival. Knockdown of the predominant PI3-kinase isoform p110δ in c-Kit/D816V-expressing Ba/F3 cells led to reduced cell transformation both in vitro and in vivo without affecting the overall PI3-kinase activity. This suggests that p110δ has a lipid-kinase-independent role in c-Kit/D816V-mediated cell transformation. We furthermore demonstrate that p110δ is phosphorylated at residues Y524 and S1039 and that phosphorylation requires an intact binding site for PI3-kinase in c-Kit/D816V. Overexpression of p110δ carrying the Y523F and S1038A mutations significantly reduced c-Kit/D816V-mediated cell survival and proliferation. Taken together, our results demonstrate an important lipid-kinase-independent role of p110δ in c-Kit/D816V-mediated cell transformation. This furthermore suggests that p110δ could be a potential diagnostic factor and selective therapeutic target for c-Kit/D816V-expressing malignancies.
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