ArticleThe Journal of biological chemistry2013
Phosphorylation of serine palmitoyltransferase long chain-1 (SPTLC1) on tyrosine 164 inhibits its activity and promotes cell survival.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- An integrative approach to studying sphingolipid metabolism reveals p53 as a master regulator of the pathway.Journal of lipid research · 2026Article
- Effect ofWorld journal of diabetes · 2025Article
- Application of Graph Models to the Identification of Transcriptomic Oncometabolic Pathways in Human Hepatocellular Carcinoma.Biomolecules · 2024Article
- E2F2 serves as an essential prognostic biomarker and therapeutic target for human renal cell carcinoma by presenting "E2F2/miR-16-5p/SPTLC1" schema.Translational oncology · 2023Article
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Structural insights into the regulation of human serine palmitoyltransferase complexes.Nature structural & molecular biology · 2021Article
- An IntegrativeIranian journal of biotechnology · 2020Article
- Sphingolipid biosynthesis in man and microbes.Natural product reports · 2018Review
- Major apoptotic mechanisms and genes involved in apoptosis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies.Molecules and cells · 2015Review
- Expression of the ORMDLS, modulators of serine palmitoyltransferase, is regulated by sphingolipids in mammalian cells.The Journal of biological chemistry · 2015Article
- Palmitoyl-ceramide accumulation with necrotic cell death in A549 cells, followed by a steep increase in sphinganine content.Biochimie open · 2015Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In BCR-ABL-expressing cells, sphingolipid metabolism is altered. Because the first step of sphingolipid biosynthesis occurs in the endoplasmic reticulum (ER), our objective was to identify ABL targets in the ER. A phosphoproteomic analysis of canine pancreatic ER microsomes identified 49 high scoring phosphotyrosine-containing peptides. These were then categorized in silico and validated in vitro. We demonstrated that the ER-resident human protein serine palmitoyltransferase long chain-1 (SPTLC1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at Tyr(164) by the tyrosine kinase ABL. Inhibition of BCR-ABL using either imatinib or shRNA-mediated silencing led to the activation of SPTLC1 and to increased apoptosis in both K562 and LAMA-84 cells. Finally, we demonstrated that mutation of Tyr(164) to Phe in SPTLC1 increased serine palmitoyltransferase activity. The Y164F mutation also promoted the remodeling of cellular sphingolipid content, thereby sensitizing K562 cells to apoptosis. Our observations provide a mechanistic explanation for imatinib-mediated cell death and a novel avenue for therapeutic strategies.
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