ArticleThe Journal of biological chemistry2010
Sphingosine interaction with acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) regulates PP2A activity and cyclooxygenase (COX)-2 expression in human endothelial cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A.The EMBO journal · 2025Article
- Deficiency of the sphingosine-1-phosphate (S1P) transporter Mfsd2b protects the heart against hypertension-induced cardiac remodeling by suppressing the L-type-CaBasic research in cardiology · 2024Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Sphingosine-1-phosphate suppresses GLUT activity through PP2A and counteracts hyperglycemia in diabetic red blood cells.Nature communications · 2023Article
- Review
- Neutral ceramidase-dependent regulation of macrophage metabolism directs intestinal immune homeostasis and controls enteric infection.Cell reports · 2022Article
- Review
- Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction.International journal of molecular sciences · 2020Article
- Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer.Respiratory research · 2019Review
- Stoichiogenomics reveal oxygen usage bias, key proteins and pathways associated with stomach cancer.Scientific reports · 2019Article
- Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs.Molecular & cellular proteomics : MCP · 2019Article
- Differential Splicing of ANP32A in Birds Alters Its Ability to Stimulate RNA Synthesis by Restricted Influenza Polymerase.Cell reports · 2018Article
- Effects of cyclopiazonic acid and dexamethasone on serotonin-induced calcium responses in vascular smooth muscle cells.Journal of physiology and biochemistry · 2016Article
- The emerging role of FTY720 (Fingolimod) in cancer treatment.Oncotarget · 2016Review
- All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase.The FEBS journal · 2016Review
- The expression and distributions of ANP32A in the developing brain.BioMed research international · 2015Article
- Cracking the ANP32 whips: important functions, unequal requirement, and hints at disease implications.BioEssays : news and reviews in molecular, cellular and developmental biology · 2014Article
- Re-configuration of sphingolipid metabolism by oncogenic transformation.Biomolecules · 2014Review
- Overexpression of the pp32r1 (ANP32C) oncogene or its functional mutant pp32r1Y140H confers enhanced resistance to FTY720 (Finguimod).Cancer biology & therapy · 2014Article
- Regulation of PP2A by Sphingolipid Metabolism and Signaling.Frontiers in oncology · 2014Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Sphingolipid metabolites regulate cell fate by acting on specific cellular targets. Although the influence of sphingolipids in cellular signaling has been well recognized, the exact molecular targets and how these targets influence cellular signaling mechanisms remain poorly understood. Toward this goal, we used affinity chromatography coupled with proteomics technology and identified acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), an inhibitor of protein phosphatase 2A (PP2A) as a direct target of sphingosine, N,N'-dimethyl sphingosine (DMS) and phytosphingosine but not dihydrosphingosine or sphingosine 1-phosphate. Treatment of human umbilical vein endothelial cells (HUVEC) with DMS, which is not phosphorylated by sphingosine kinases, led to the activation of PP2A activity. Suppression of ANP32A with siRNA enhanced basal and DMS-activated PP2A activity suggesting that the sphingoid base binds to and relieves the inhibitory action of ANP32A on the PP2A complex. Indeed, DMS relieved the ANP32A-mediated inhibition of PP2A enzyme complex in vitro. Interestingly, DMS treatment induced the p38 stress-activated protein kinase (SAPK) and expression of cyclooxygenase (COX)-2 transcript and protein. Knockdown of ANP32A expression further induced p38 SAPK and COX-2. These data identify ANP32A as a novel molecular target of sphingoid bases that regulates cellular signaling events and inflammatory gene expression.
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