ArticleProceedings of the National Academy of Sciences of the United States of America2019
Phosphorylation-mediated activation of mouse Xkr8 scramblase for phosphatidylserine exposure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 64 citations in OpenAlex.
- Macrophage efferocytosis promotes inflammation resolution and accelerates wound healing.Communications biology · 2026Review
- Lipid asymmetry disruption by XKR8 orchestrates neutrophil extracellular trap formation and inhibits fungal infection.Nature immunology · 2026Article
- Irgm1 Improves Postinfarction Cardiac Repair by Promoting Neutrophil Clearance and Efferocytosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phospholipid scramblases TMEM16F and Xkr8 mediate distinct features of phosphatidylserine (PS) externalization and immune suppression to promote tumor growth.Cell death discovery · 2025Article
- The potential of efferocytosis for the treatment of bronchial asthma: A review of current trends, mechanisms and prospects.Biochemistry and biophysics reports · 2025Review
- Structure and function of the human apoptotic scramblase Xkr4.Nature communications · 2025Article
- Targeting Frequent Efferocytosis in Tumor Microenvironment is a New Direction for Cancer Treatment.Small science · 2025Review
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- "Find Me" and "Eat Me" signals: tools to drive phagocytic processes for modulating antitumor immunity.Cancer communications (London, England) · 2024Review
- Breakdown of Phospholipid Asymmetry Triggers ADAM17-Mediated Rescue Events in Cells Undergoing Apoptosis.Membranes · 2023Article
- Microparticle Phosphatidylserine Mediates Coagulation: Involvement in Tumor Progression and Metastasis.Cancers · 2023Review
- How do necrotic cells expose phosphatidylserine to attract their predators-What's unique and what's in common with apoptotic cells.Frontiers in cell and developmental biology · 2023Review
- Scrambled or flipped: 5 facts about how cellular phosphatidylserine localization can mediate viral replication.PLoS pathogens · 2022Article
- Requirement of Xk and Vps13a for the P2X7-mediated phospholipid scrambling and cell lysis in mouse T cells.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Scramblases as Regulators of ProteolyticMembranes · 2022Review
- Phosphatidylserine eversion regulated by phospholipid scramblase activated by TGF-β1/Smad signaling in the early stage of kidney stone formation.Urolithiasis · 2022Article
- Article
- Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling.eLife · 2021Article
- Review
- The Peroxisomal Localization of Hsd17b4 Is Regulated by Its Interaction with Phosphatidylserine.Molecules and cells · 2021Article
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 exposure of phosphatidylserine (PtdSer) to the cell surface is regulated by the down-regulation of flippases and the activation of scramblases. Xkr8 has been identified as a scramblase that is activated during apoptosis, but its exogenous expression in the mouse Ba/F3 pro B cell line induces constitutive PtdSer exposure. Here we found that this Xkr8-mediated PtdSer exposure occurred at 4 °C, but not at 20 °C, although its scramblase activity was observed at 20 °C. The Xkr8-mediated PtdSer exposure was inhibited by a kinase inhibitor and enhanced by phosphatase inhibitors. Phosphorylated Xkr8 was detected by Phos-tag PAGE, and a mass spectrometric and mutational analysis identified three phosphorylation sites. Their phosphomimic mutation rendered Xkr8 resistant to the kinase inhibitor for PtdSer exposure at 4 °C, but unlike phosphatase inhibitors, it did not induce constitutive PtdSer exposure at 20 °C. On the other hand, when the flippase genes were deleted, the Xkr8 induced constitutive PtdSer exposure at high temperature, indicating that the flippase activity normally counteracted Xkr8's ability to expose PtdSer. These results indicate that PtdSer exposure can be increased by the phosphorylation-mediated activation of Xkr8 scramblase and flippase down-regulation.
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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.